The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index; 6 of the 89 sources its claims cite were checked for support.
Regulation of Lymphoid Enhancer Factor 1/T-Cell Factor by Mitogen-Activated Protein Kinase-Related Nemo-Like Kinase-Dependent Phosphorylation in Wnt/β-Catenin Signaling
Open accessAbstract
The Wnt/beta-catenin signaling pathway regulates many developmental processes by modulating gene expression. Wnt signaling induces the stabilization of cytosolic beta-catenin, which then associates with lymphoid enhancer factor and T-cell factor (LEF-1/TCF) to form a transcription complex that activates Wnt target genes. Previously, we have shown that a specific mitogen-activated protein (MAP) kinase pathway involving the MAP kinase kinase kinase TAK1 and MAP kinase-related Nemo-like kinase (NLK) suppresses Wnt signaling. In this study, we investigated the relationships among NLK, beta-catenin, and LEF-1/TCF. We found that NLK interacts directly with LEF-1/TCF and indirectly with beta-catenin via LEF-1/TCF to form a complex. NLK phosphorylates LEF-1/TCF on two serine/threonine residues located in its central region. Mutation of both residues to alanine enhanced LEF-1 transcriptional activity and rendered it resistant to inhibition by NLK. Phosphorylation of TCF-4 by NLK inhibited DNA binding by the beta-catenin-TCF-4 complex. However, this inhibition was abrogated when a mutant form of TCF-4 was used in which both threonines were replaced with valines. These results suggest that NLK phosphorylation on these sites contributes to the down-regulation of LEF-1/TCF transcriptional activity.
Overview
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Written from the paper’s full text.
TL;DR
NLK directly binds LEF-1/TCF and phosphorylates conserved central serine/threonine residues, thereby inhibiting β-catenin–TCF DNA binding and LEF-1/TCF transcriptional activity. β-Catenin associates with NLK indirectly through LEF-1/TCF, and β-catenin enhances NLK phosphorylation of TCF-4.
Key findings
- NLK interacted directly with LEF-1/TCF but not appreciably with β-catenin; LEF-1/TCF bridged β-catenin to NLK, and β-catenin enhanced NLK phosphorylation of TCF-4 in vitro.
- NLK phosphorylated LEF-1 at Thr-155 and Ser-166 and TCF-4 at Thr-178 and Thr-189; LEF-1(2A) and TCF-4(2V) mutants showed greatly reduced NLK phosphorylation.
- LEF-1(2A) enhanced Wnt-1-induced TOPFLASH reporter activity more strongly than wild-type LEF-1 and was resistant to NLK inhibition; Wnt-1 alone induced the reporter about fourfold.
- NLK phosphorylation of TCF-4 inhibited DNA binding by the β-catenin–TCF-4 complex, while TCF-4(2V) enhanced DNA binding and remained bound even with NLK expression.
Methods
- Biochemical and cell-based study using human embryonic kidney 293 and HeLa cells, with transfected Flag-NLK, T7/HA-LEF-1, TCF-4, β-catenin, and mutant constructs.
- Assays included yeast two-hybrid, coimmunoprecipitation/immunoblotting, in vitro kinase assays with [γ-32P]ATP, TOPFLASH/FOPFLASH luciferase reporter assays, and gel mobility shift assays.
- Main analysis compared wild-type versus phosphorylation-site mutants LEF-1(2A) and TCF-4(2V) for NLK binding, phosphorylation, β-catenin association, transcriptional activity, and DNA binding.
Limitations
- Stated in the paper: weak residual phosphorylation of LEF-1(2A) and TCF-4(2V) suggests additional NLK phosphorylation sites may exist; NLK overexpression failed to suppress endogenous LEF-1/TCF-dependent transcription in HeLa cells, suggesting a resistant complex.
- Evident from the text: mechanistic conclusions rely heavily on overexpression in 293/HeLa cell lines and in vitro kinase/gel-shift assays, with no vertebrate in vivo requirement for these phosphorylation sites tested here.
- Evident from the text: the mechanism by which NLK phosphorylation distal to the DNA-binding domain inhibits β-catenin–TCF-4 DNA binding was not determined.
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Claims the paper makes
57 Own result · 54 No full text of the sources · 41 Own interpretation · 2 Supported so far · 2 Partly supported · 1 Not supported · 1 Not checked yet · 1 No basis given · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Indeed, WRM-1, which is only 19% identical to vertebrate β-catenin, does not bind to the POP-1 β-catenin-binding domain per se but weakly binds full-length POP-1 (14, 19, 22).”
What the sources say
- Not checked — no full text of the sourcecites [14] source
- Disputedcites [19] sourceExperimental — accuracy not yet measured
The percentage-identity table in the section on β-catenin family members across species (page unavailable) gives 17% identity between WRM-1 and human β-catenin, not 19%. The Methods section says these percentages were calculated from sequence alignments. (LLM, conf=0.90)
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- Not checked — no full text of the sourcecites [22] source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“HeLa cells, which contain low levels of endogenous LEF-1/TCF (10).”
What the sources say
- Partly supportedcites [10] sourceExperimental — accuracy not yet measured
The Results (page not provided) describe HeLa cells as not expressing LEF-1, supporting low endogenous LEF-1 relative to LEF-1-expressing Jurkat cells. The passage does not establish the level of endogenous TCF in HeLa cells. (LLM, conf=0.82)
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- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Indeed, WRM-1, which is only 19% identical to vertebrate β-catenin, does not bind to the POP-1 β-catenin-binding domain per se but weakly binds full-length POP-1 (14, 19, 22).”
What the sources say
- Not checked — no full text of the sourcecites [14] source
- Partly supportedcites [19] sourceExperimental — accuracy not yet measured
In the protein-interaction results (page unavailable), WRM-1 interacts weakly with POP-1 even after deletion of POP-1’s amino-terminal β-catenin-binding region. This supports an interaction that does not require that region, but the paper does not test whether WRM-1 can bind the region itself; it presents a different mode of interaction as a suggestion, not a categorical finding. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [22] source
plain- Asserted: passes — The authors put it forward as true.
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The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Indeed, WRM-1, which is only 19% identical to vertebrate β-catenin, does not bind to the POP-1 β-catenin-binding domain per se but weakly binds full-length POP-1 (14, 19, 22).”
What the sources say
- Not checked — no full text of the sourcecites [14] source
- Supportedcites [19] source
In the β-catenin family members across species section, the POP-1 interaction table records a weak WRM-1 interaction with full-length POP-1; the accompanying text explicitly calls it a weak interaction. The finding comes from a yeast interaction assay, so “binds” is a paraphrase of that result. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [22] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NLK phosphorylates LEF-1/TCF on two serine/threonine residues located in its central region.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Mutation of both residues to alanine enhanced LEF-1 transcriptional activity and rendered it resistant to inhibition by NLK.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Mutation of both residues to alanine enhanced LEF-1 transcriptional activity and rendered it resistant to inhibition by NLK.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“We found that NLK interacts directly with LEF-1/TCF and indirectly with β-catenin via LEF-1/TCF to form a complex.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“We found that NLK interacts directly with LEF-1/TCF and indirectly with β-catenin via LEF-1/TCF to form a complex.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Phosphorylation of TCF-4 by NLK inhibited DNA binding by the β-catenin-TCF-4 complex.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“However, this inhibition was abrogated when a mutant form of TCF-4 was used in which both threonines were replaced with valines.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In vitro kinase reactions showed that phosphorylation of TCF-4(2V) by NLK was greatly decreased in comparison with that of wild-type TCF-4 (Fig. 4C, top panel, lanes 1 and 3).”
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In the paper
“Stimulation with Wnt-1 induced expression of this reporter gene about fourfold over that of the vector-transfected cells (Fig. 6, lanes 1 and 4).”
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In the paper
“In contrast, no activity was observed when a FOPFLASH reporter, which lacks LEF-1/TCF-binding sites, was cotransfected (Fig. 6, lane 14).”
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In the paper
“We observed that Flag-NLK and T7-LEF-1ΔN could interact when coexpressed (Fig. 1, top panel, lane 8), indicating that the NH2-terminal deletion of LEF-1 does not affect its association with NLK.”
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In the paper
“LEF-1 was found to associate with NLK (Fig. 1, top panel, lane 6).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“whereas coexpression of the kinase-negative mutant form NLK(K155M) did not (Fig. 6, lane 8).”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In this assay, NLK was found to associate with both LEF-1ΔN and LEF-1ΔC (Fig. 3, top panel, lanes 5 and 6).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed that, in the absence of exogenous TCF-4, little β-catenin was detected in the NLK immunocomplexes precipitated with the anti-Flag antibody (Fig. 2, second panel, lane 3).”
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In the paper
“As shown in Fig. 3B, NLK phosphorylated both LEF-1ΔN and LEF-1ΔC in vitro (Fig. 3, bottom panel, lanes 5 and 6) and this phosphorylation was dependent on the kinase activity of NLK (Fig. 3, bottom panel, lanes 8 and 9).”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed that coexpression of LEF-1 dramatically increased the interaction between β-catenin and NLK (Fig. 1, middle panel, lane 7).”
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In the paper
“We identify two NLK phosphorylation sites in LEF-1/TCF and present data suggesting that phosphorylation of these sites contributes to the down-regulation of LEF-1/TCF transcriptional activity.”
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In the paper
“However, when TCF-4 was coexpressed, the amount of β-catenin detected in the immunocomplexes increased (Fig. 2, second panel, lane 5).”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Expression of the mutant form LEF-1(2A) alone did not activate the reporter (Fig. 6, lane 3)”
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In the paper
“Wild-type LEF-1 was efficiently phosphorylated by active but not inactive NLK (Fig. 4B, top panel, lanes 1 and 2).”
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In the paper
“On the other hand, the mutated LEF-1(2A) protein was only weakly phosphorylated by NLK (Fig. 4B, top panel, lane 3).”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“When NLK was coexpressed with Wnt-1 and LEF-1, it inhibited reporter activity (Fig. 6, lane 7)”
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In the paper
“This analysis revealed that NLK association with LEF-1(2A) (Fig. 5, top panel, lane 4) and TCF-4(2V) (Fig. 5, top panel, lane 8) was normal”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Western blot analysis revealed that the LEF-1 and TCF-4 proteins migrated more slowly on SDS-PAGE when wild-type NLK was coexpressed (Fig. 4D, lanes 2 and 7).”
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In the paper
“As shown in Fig. 3B, NLK phosphorylated both LEF-1ΔN and LEF-1ΔC in vitro (Fig. 3, bottom panel, lanes 5 and 6) and this phosphorylation was dependent on the kinase activity of NLK (Fig. 3, bottom panel, lanes 8 and 9).”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the present report, we show that NLK directly interacts with and phosphorylates LEF-1/TCF.”
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In the paper
“Expression of the kinase-negative mutant NLK(K155M) failed to cause mobility shifts of LEF-1 (lane 3) and TCF-4 (lane 8).”
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In the paper
“Furthermore, when LEF-1(2A) or TCF-4(2V) was coexpressed along with NLK, a fractional shift was observed (lanes 5 and 10)”
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In the paper
“In contrast, NLK association with β-catenin was barely detectable (Fig. 1, middle panel, lane 5).”
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In the paper
“We found that the mutated forms of LEF-1 and TCF-4 associated with β-catenin to the same extent as each of the respective wild-type forms”
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In the paper
“However, cotransfection of β-catenin enhanced NLK phosphorylation of TCF-4 (Fig. 2, bottom panel, lane 5).”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“but coexpression of LEF-1(2A) with Wnt-1 stimulated Wnt-1-induced reporter activity more strongly than did expression of wild-type LEF-1 (Fig. 6, lane 9).”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“A kinase-negative form of NLK, NLK(K155M), also interacted with LEF-1, LEF-1ΔN, and LEF-1ΔC (Fig. 3, top panel, lanes 7 to 9).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Examination of the primary sequences of the LEF-1/TCF middle regions revealed two potential NLK phosphorylation sites that are conserved among human LEF-1, human TCF-4, and C. elegans POP-1 (Fig. 4A).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Precipitation of LEF-1(2A) with NLK was normal (Fig. 4B, middle panel, lane 3)”
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In the paper
“In a parallel experiment, LEF-1 was not observed to cause such enhancement (data not shown).”
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In the paper
“However, coexpression of LEF-1 and Wnt-1 enhanced Wnt-1-induced activation of the reporter (Fig. 6, lane 6).”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“We confirmed this interaction by coexpressing Flag-NLK and TCF-4 in 293 cells (Fig. 2, top panel, lane 4).”
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The binding of NLK to LEF-1 was also detected by using a yeast two-hybrid system (data not shown), supporting the idea that the interaction between these two proteins is direct.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, coexpression of LEF-1ΔN did not enhance the association between NLK and β-catenin (Fig. 1, middle panel, lane 9), as had been observed with wild-type LEF-1.”
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Expression of LEF-1 alone did not augment the activation of the reporter gene (lane 2).”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“As observed previously (13), NLK phosphorylated TCF-4 in vitro even in the absence of β-catenin transfection (Fig. 2, bottom panel, lane 4).”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Western blot analysis confirmed that neither mutation of TCF-4 to TCF-4(2V) nor phosphorylation of TCF-4 by NLK affected its interaction with β-catenin in vitro (Fig. 7A).”
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, NLK did not inhibit reporter activity induced by coexpression of LEF-1(2A) with Wnt-1 (Fig. 6, lane 10).”
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Western blot analysis confirmed that neither mutation of TCF-4 to TCF-4(2V) nor phosphorylation of TCF-4 by NLK affected its interaction with β-catenin in vitro (Fig. 7A).”
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As expected, this band was supershifted by anti-β-catenin (lane 5) and anti-TCF-4 (lane 9) antibodies, confirming that it contained the β-catenin-TCF-4-DNA complex.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Specifically, these sites mapped, in vitro and in vivo, to Thr-155 and Ser-166 of LEF-1 and Thr-178 and Thr-189 of TCF-4.”
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, when nuclear extracts containing β-catenin were mixed with those prepared from cells coexpressing wild-type TCF-4 and NLK, the formation of the β-catenin-TCF-4-DNA complex was greatly reduced (Fig. 7B, lane 3).”
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, in vertebrates, LEF-1/TCF binds directly to NLK and β-catenin interacts indirectly with NLK via LEF-1/TCF to form a larger complex.”
- Also stated in: § DISCUSSION · hedged
“Our observation that NLK interacts directly with LEF-1/TCF makes it likely that LIT-1 would interact directly with POP-1 in the control of T-cell polarity.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Also stated in: § DISCUSSION · hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, the mutant TCF-4(2V)-β-catenin complex remained bound to DNA even when NLK was expressed (Fig. 7B, lane 4)”
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As shown in lane 2, we found that the TCF-4(2V) mutation actually enhanced DNA-binding activity.”
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Site-directed mutagenesis of these conserved serine and threonine residues abrogated NLK-mediated phosphorylation in vitro and in vivo.”
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A specific band was detected when mixtures of nuclear extracts containing wild-type TCF-4 and β-catenin were incubated with the probe (Fig. 7B, lane 1).”
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NLK overexpression failed to suppress the endogenous LEF-1/TCF-dependent transcription (lanes 4 and 5).”
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this study, we found that the primary sites of NLK phosphorylation are located in the core region between the β-catenin-binding domain and the DNA-binding domain in the LEF-1 and TCF-4 proteins.”
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mutational replacement of these serine and threonine residues with alanine or valine prevents NLK-mediated negative regulation of LEF-1 and TCF-4.”
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this report, we identify two NLK phosphorylation sites in LEF-1 and TCF-4”
plain- Asserted: passes — The authors put it forward as true.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Thus, a MAPK-related pathway acts in concert with Wnt signaling to establish anterior-posterior polarity in C. elegans.”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The lit-1 gene encodes a mitogen-activated protein kinase (MAPK)-like protein similar to the Drosophila Nemo protein kinase and the mouse Nemo-like kinase (NLK).”
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Furthermore, MOM-4 can activate kinase activity of the LIT-1-WRM-1 complex (27).”
What the sources say
- Not checked — no full text of the sourcecites [27] Shin T. H., 1999, Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The mom-4 gene encodes a MAPK kinase kinase-like protein related to the mammalian protein kinase TAK1.”
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Mutations in lit-1 or mom-4 cause a loss of polarity and POP-1 asymmetry (16, 22, 27).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that NLK phosphorylation on these sites contributes to the down-regulation of LEF-1/TCF transcriptional activity.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“whereas in C. elegans, WRM-1 down-regulates, rather than activates, POP-1 (16, 21, 22, 30).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Recent evidence indicates that the Wnt signaling pathway in mammalian cells is also regulated by a MAPK-related pathway composed of MAPK kinase kinase TAK1 and MAPK-related NLK (13).”
What the sources say
- Not checked — no full text of the sourcecites [13] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, TAK1 and NLK are negative regulators of LEF-1/TCF activity.”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Previously, we have shown that a specific mitogen-activated protein (MAP) kinase pathway involving the MAP kinase kinase kinase TAK1 and MAP kinase-related Nemo-like kinase (NLK) suppresses Wnt signaling.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that β-catenin is recruited to the NLK-LEF-1 complex via interaction with the NH2 terminus of LEF-1.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“β-Catenin forms a complex with NLK in a LEF-1/TCF-dependent manner.”
- Also stated in: § RESULTS · hedged
“These results suggest that LEF-1 binds directly to NLK, while β-catenin interacts indirectly with NLK via binding to LEF-1.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § RESULTS · hedged
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed that Flag-NLK and T7-LEF-1ΔN could interact when coexpressed (Fig. 1, top panel, lane 8), indicating that the NH2-terminal deletion of LEF-1 does not affect its association with NLK.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, TAK1-NLK and MOM-4-LIT-1 appear to function analogously to regulate Wnt signaling pathways in mammalian cells and C. elegans, respectively.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that mutations at the sites of NLK phosphorylation probably do not alter the global three-dimensional structure of LEF-1 or TCF-4.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This indicates that NLK inhibits LEF-1-dependent activation of the LEF-1/TCF reporter”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NLK directly interacts with LEF-1/TCF but not with β-catenin.”
- Also stated in: § RESULTS · hedged
“In contrast, NLK association with β-catenin was barely detectable (Fig. 1, middle panel, lane 5).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § RESULTS · hedged
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results are consistent with the idea that NLK phosphorylates LEF-1 and TCF-4 at these serine/threonine residues in vivo.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that the LEF-1(2A) mutation does not affect its interaction with NLK in vitro.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that the NLK phosphorylation sites are also located in the middle region between the β-catenin-binding domain and the DNA-binding domain of LEF-1.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
In the paper
“We have previously shown that NLK interacts with the β-catenin-LEF-1/TCF complex (13).”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A small deletion removing the NH2-terminal 62 amino acids of LEF-1 (LEF-1ΔN) abrogated its interaction with β-catenin (data not shown) (2).”
What the sources say
- Not checked — no full text of the sourcecites [2] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that the full mobility shift requires phosphorylation of both sites.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This supports the possibility that LEF-1/TCF forms a bridge between β-catenin and NLK.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that NLK catalyzes the phosphorylation of Thr-155 and Ser-166 in LEF-1 in vitro.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
In the paper
“We have previously shown that NLK associates with TCF-4 (13).”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“These mobility shifts were shown to be due to phosphorylation (13).”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This result indicates that the middle region of LEF-1 contributes to NLK interaction.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
In the paper
“β-Catenin binds to a region within the NH2-terminal region of LEF-1/TCF (see Fig. 3A) (2).”
What the sources say
- Not checked — no full text of the sourcecites [2] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests that NLK phosphorylates at least the Thr-178 and Thr-189 sites of TCF-4 in vitro.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We identify two NLK phosphorylation sites in LEF-1/TCF and present data suggesting that phosphorylation of these sites contributes to the down-regulation of LEF-1/TCF transcriptional activity.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests that NLK may phosphorylate the β-catenin-TCF-4 complex more efficiently than TCF-4.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The fact that some weak phosphorylation was still observed with the LEF-1(2A) and TCF-4(2V) mutant forms suggests that LEF-1 and TCF-4 may contain additional NLK phosphorylation sites.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the present report, we show that NLK directly interacts with and phosphorylates LEF-1/TCF.”
- Also stated in: § RESULTS · plain
“NLK directly interacts with LEF-1/TCF but not with β-catenin.”
- Also stated in: § RESULTS · hedged
“These results suggest that LEF-1 binds directly to NLK, while β-catenin interacts indirectly with NLK via binding to LEF-1.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § RESULTS · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that TAK1 and NLK act in a pathway parallel to the Wnt pathway.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Although LIT-1 controls both EMS and T-cell polarities, neither WRM-1 nor any other β-catenin homolog is involved in T-cell polarity (9).”
What the sources say
- Not checked — no full text of the sourcecites [9] Herman M. C., 2001, Development source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The C. elegans LIT-1 protein interacts directly with WRM-1, and this complex can phosphorylate POP-1 in a manner that requires the LIT-1 kinase domain (22).”
What the sources say
- Not checked — no full text of the sourcecites [22] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that NLK phosphorylation of the two sites on wild-type TCF-4 causes decreased DNA binding.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Although LIT-1 controls both EMS and T-cell polarities, neither WRM-1 nor any other β-catenin homolog is involved in T-cell polarity (9).”
What the sources say
- Not checked — no full text of the sourcecites [9] Herman M. C., 2001, Development source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This indicates that WRM-1 is required for POP-1 phosphorylation.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results support a model whereby phosphorylation of Thr-178 and Thr-189 in TCF-4 mediates the inhibitory effect of NLK.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and that this inhibition requires NLK kinase activity.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In particular, C. elegans WRM-1 appears to possess important functional differences from other family members.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The components of the Wnt pathway (β-catenin, LEF-1/TCF, NLK) are conserved in vertebrates.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“POP-1, a LEF-1/TCF-related protein, functions to repress gene expression, and Wnt signaling down-regulates the activity of POP-1 (15, 16, 21, 22, 30).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests that HeLa cells may contain an LEF-1/TCF complex that is resistant to NLK-mediated repression.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, in vertebrates, LEF-1/TCF binds directly to NLK and β-catenin interacts indirectly with NLK via LEF-1/TCF to form a larger complex.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The presence of β-catenin enhances the interaction between NLK and TCF-4 and thereby promotes phosphorylation of TCF-4 by NLK.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“POP-1 plays a negative role in Wnt signaling and is inhibited by WRM-1 through LIT-1-mediated phosphorylation of POP-1 (22).”
What the sources say
- Not checked — no full text of the sourcecites [22] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Thus, WRM-1 and POP-1, rather than working as cofactors, have opposing functions.”
What the sources say
- Not checked — no full text of the sourcecites [22] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that the repression of LEF-1 activity by NLK requires the two phosphorylation sites in LEF-1.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Thus, as observed previously (13), NLK phosphorylation of TCF-4 prevents the β-catenin-TCF-4 complex from binding DNA.”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The presence of β-catenin enhances the interaction between NLK and TCF-4 and thereby promotes phosphorylation of TCF-4 by NLK.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“POP-1, a LEF-1/TCF-related protein, functions to repress gene expression, and Wnt signaling down-regulates the activity of POP-1 (15, 16, 21, 22, 30).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This indicates that NLK expression interferes with the assembly of the complex.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our observation that NLK interacts directly with LEF-1/TCF makes it likely that LIT-1 would interact directly with POP-1 in the control of T-cell polarity.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The components of the Wnt pathway (β-catenin, LEF-1/TCF, NLK) are conserved in vertebrates.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although we have not determined the mechanism for inhibition of the β-catenin-TCF-4 complex DNA binding by NLK-mediated threonine phosphorylation, it is presumably not caused by direct phosphorylation of the DNA-binding domain, since the sites of NLK phosphorylation are located distal to the DNA-binding domain.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: In many cases in which phosphorylation inhibits DNA binding, the phosphorylation sites are located either within or near the DNA-binding domain.
- Rests on an assumption: In such cases, phosphorylation interferes with DNA binding by electrostatic repulsion between phosphate groups on the protein and the DNA.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“present data suggesting that phosphorylation of these sites contributes to the down-regulation of the ability of LEF-1/TCF transcriptional activity.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“yet it does prevent DNA binding of the β-catenin-TCF-4 complex”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“We have previously demonstrated that NLK can regulate the transcriptional activity of a β-catenin-LEF-1/TCF complex (13).”
What the sources say
- Not checked — no full text of the sourcecites [13] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“This phosphorylation does not disrupt the formation of a complex between LEF-1/TCF and β-catenin”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Phosphorylation inhibits LEF-1/TCF signaling by disruption of DNA binding (13)”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Since Xenopus NLK is expressed ubiquitously as both a maternal and a zygotic transcript in Xenopus embryos (11)”
What the sources say
- Not checked — no full text of the sourcecites [11] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“and by inducing redistribution of POP-1 from the nucleus to the cytoplasm (22).”
What the sources say
- Not checked — no full text of the sourcecites [22] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, it is likely that β-catenin signaling through LEF-1/TCF is inhibited by several mechanisms at the level of LEF-1/TCF and β-catenin in the nucleus.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Furthermore, in both C. elegans and mammalian cells, the Nemo-like kinases LIT-1 and NLK, respectively, phosphorylate LEF-1/TCF.”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“and thereby inhibits β-catenin-mediated transcription through LEF-1/TCF-binding sites in Wnt pathway-responsive promoters.”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In vivo, coinjection of NLK RNA into early Xenopus embryos results in the inhibition of double-axis formation by β-catenin.”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 17
- It may state two separate claims as one. 17
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“β-Catenin then translocates into the nucleus, where it forms a complex with the HMG box class of transcription factors, including lymphoid enhancer factor 1 (LEF-1) and T-cell factor (TCF), and activates the transcription of its target genes (5, 17, 20).”
What the sources say
- Supportedcites [5] source
The “Binding of Arm/β-catenin to Tcf-LEF-1” section (page not specified) says β-catenin accumulates in the nucleus after Wnt stimulation, binds HMG-box factors of the Tcf-LEF-1 family, and forms complexes that activate transcription. This supports the cited paraphrase. (LLM, conf=0.93)
- Supportedcites [17] source
The section on nuclear β-catenin says LEF-1 and XTcf-3, both HMG-box factors, bind β-catenin and translocate it to the nucleus. The Figure 3 discussion says the resulting complex binds DNA and alters transcription; the paper also reports transactivation of a reporter gene. Page numbers are not supplied in our copy. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [20] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Supported
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“These results suggest that Wnt signaling and the MAPK-related cascade both act to control polarity by regulating POP-1 and that integration of two signals occurs at the level of complex formation between WRM-1 and LIT-1.”
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“TAK1 functions upstream of NLK and enhances NLK kinase activity.”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Active NLK phosphorylates LEF-1/TCF and prevents the β-catenin-TCF complex from binding to DNA, thereby inhibiting the ability of β-catenin-TCF to activate transcription.”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“LIT-1 interacts directly with WRM-1, and this complex can phosphorylate POP-1 in a LIT-1 kinase domain-dependent manner, indicating that these pathways converge at WRM-1 (22).”
What the sources say
- Not checked — no full text of the sourcecites [22] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Consistent with this, ectopic expression of NLK blocks double-axis formation in Xenopus induced by overexpression of β-catenin but not by the downstream components siamois and twin (13).”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In this complex, LEF-1/TCF provides the DNA-binding domain while β-catenin contributes the transactivation domain, allowing the activation of LEF-1/TCF target genes.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Although LEF-1/TCF family members share overall sequence similarity, these two regions are particularly conserved (18).”
What the sources say
- Not checked — no full text of the sourcecites [18] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In C. elegans, WRM-1 and LIT-1 appear to form a stable protein complex in vivo (22).”
What the sources say
- Not checked — no full text of the sourcecites [22] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In C. elegans, WRM-1 (β-catenin) directly interacts with and activates LIT-1 (NLK).”
What the sources say
- Not checked — no full text of the sourcecites [22] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Active LIT-1 then phosphorylates WRM-1 and POP-1 (LEF-1/TCF) (22).”
What the sources say
- Not checked — no full text of the sourcecites [22] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“S/TP motifs are consensus sites for MAPK phosphorylation (31).”
What the sources say
- Not checked — no full text of the sourcecites [31] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“LEF-1/TCF has been shown to form a complex with β-catenin in response to Wnt stimulation (2, 4, 18, 34).”
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Although LEF-1/TCF family members share overall sequence similarity, these two regions are particularly conserved (18).”
What the sources say
- Not checked — no full text of the sourcecites [18] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, these results do not completely rule out the possibility that these residues play a role in the association of LEF-1 and TCF-4 with NLK.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“WRM-1 activates the LIT-1 protein kinase, leading to phosphorylation of WRM-1, LIT-1, and POP-1.”
What the sources say
- Not checked — no full text of the sourcecites [22] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that the LEF-1(2A) and TCF-4(2V) mutations abrogate phosphorylation per se and do not otherwise affect the interaction with NLK in vivo.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
In the paper
“Rocheleau et al. (22) have demonstrated that the WRM-1 protein binds to and activates LIT-1.”
What the sources say
- Not checked — no full text of the sourcecites [22] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“T-cell polarity is controlled by LIN-44 (Wnt), LIN-17 (Frizzled receptor), and POP-1 (7, 8, 9, 26).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings indicate that the components of the Wnt pathway in C. elegans and vertebrates are similar but have different activities.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The components of the Wnt pathway (β-catenin, LEF-1/TCF, NLK) are conserved in vertebrates.
In the paper
“POP-1 plays a negative role in Wnt signaling and is inhibited by WRM-1 through LIT-1-mediated phosphorylation of POP-1 (22).”
What the sources say
- Not checked — no full text of the sourcecites [22] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The β-catenin-LEF-1/TCF complex, in turn, activates Wnt target genes in the nucleus (2, 4, 18, 34).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“On the other hand, β-catenins can stably bind to LEF-1/TCF (2).”
What the sources say
- Not checked — no full text of the sourcecites [2] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is likely that functionally conserved serine and threonine residues are also present between the β-catenin-binding domain and the DNA-binding domain of LEF-1/TCF that regulate its activity.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The C. elegans LIT-1 protein interacts directly with WRM-1, and this complex can phosphorylate POP-1 in a manner that requires the LIT-1 kinase domain (22).”
What the sources say
- Not checked — no full text of the sourcecites [22] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This activation leads to the phosphorylation of POP-1 and apparent changes in its subcellular localization (22).”
What the sources say
- Not checked — no full text of the sourcecites [22] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“We have previously shown that NLK phosphorylates TCF-4 and prevents the β-catenin-TCF-4 complex from binding DNA (13).”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“it has the potential both to regulate the axis-determining activity of LEF-1/TCF and to modulate other potential functions of LEF-1/TCF at later stages of development, such as neural patterning or mesoderm development (11).”
What the sources say
- Not checked — no full text of the sourcecites [11] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mechanistically, NLK directly interacts with and phosphorylates TCF-4.”
What the sources say
- Not checked — no full text of the sourcecites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Such regulation of DNA binding by phosphorylation of sequence-specific transcription factors has been well documented in several cases and can act both positively and negatively (3).”
What the sources say
- Not checked — no full text of the sourcecites [3] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
In mammalian cells, the relationships among NLK, β-catenin, and LEF-1/TCF are not well understood.
“On the other hand, in mammalian cells, the relationships among NLK, β-catenin, and LEF-1/TCF are not well understood.”
The paper relies on this without support.
The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain.
“The LEF-1 protein contains a COOH-terminal HMG DNA-binding domain and an NH2-terminal β-catenin-binding domain (Fig. 3A).”
The paper relies on this without support.
The components of the Wnt pathway (β-catenin, LEF-1/TCF, NLK) are conserved in vertebrates.
“These components are conserved in vertebrates.”
The paper relies on this without support.
In the early C. elegans embryo, Wnt signaling controls anterior-posterior cell polarity in the EMS blastomere.
“In the early C. elegans embryo, Wnt signaling controls anterior-posterior cell polarity in the EMS blastomere.”
The paper relies on this without support.
The β-catenin-related factor WRM-1 and the NLK-related kinase LIT-1 are effectors of Wnt signaling in the early C. elegans embryo.
“The β-catenin-related factor WRM-1 and the NLK-related kinase LIT-1 are effectors of this signaling pathway.”
The paper relies on this without support.
C. elegans Wnt signaling controls anterior-posterior cell polarity in postembryonic T blast cells.
“C. elegans Wnt signaling also controls anterior-posterior cell polarity in postembryonic T blast cells.”
The paper relies on this without support.
In many cases in which phosphorylation inhibits DNA binding, the phosphorylation sites are located either within or near the DNA-binding domain.
“In many cases in which phosphorylation inhibits DNA binding, the phosphorylation sites are located either within or near the DNA-binding domain.”
The paper relies on this without support.
In such cases, phosphorylation interferes with DNA binding by electrostatic repulsion between phosphate groups on the protein and the DNA.
“In such cases, it is likely that phosphorylation interferes with DNA binding by electrostatic repulsion between phosphate groups on the protein and the DNA.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In 293 cells, Flag-NLK suppressed reporter gene expression, a finding in agreement with previous reports.17), 34)”
From Mammalian Nemo-like kinase enhances .BETA.-catenin-TCF transcription activity in human osteosarcoma and neuroblastoma cells (2007) · cites this paper as [34]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Ishitani et al. suggested that DNA binding of LEF1 decreased with its phosphorylation at threonine 155 and serine 166 by overexpression of NLK.17), 34)”
From Mammalian Nemo-like kinase enhances .BETA.-catenin-TCF transcription activity in human osteosarcoma and neuroblastoma cells (2007) · cites this paper as [34]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In vertebrates, NLK is considered to be a negative regulator of the Wnt signalling pathway.”
From Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies (2020) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“This phosphorylation prevents DNA binding of the β-catenin-TCF4 complex and limits β-catenin-mediated target gene transcription through TCF/LEF [16,17].”
From Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies (2020) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“Previous studies showed that NLK can regulate the transcriptional activity of the β-catenin-LEF/TCF complex by directly phosphorylating TCF4.”
From Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies (2020) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“NLK-KN is a lysine to methionine substitution at residue 155 (K155M) and is defective for kinase activity (Ishitani et al., 2003; Ishitani et al., 2011).”
From Polyglutamine Disease Toxicity Is Regulated by Nemo-like Kinase in Spinocerebellar Ataxia Type 1 (2013) · cites this paper as Ishitani et al., 2003
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ DISCUSSION
“Site-directed mutagenesis of these conserved serine and threonine residues abrogated NLK-mediated phosphorylation in vitro and in vivo.”
§ RESULTS
“The fact that some weak phosphorylation was still observed with the LEF-1(2A) and TCF-4(2V) mutant forms suggests that LEF-1 and TCF-4 may contain additional NLK phosphorylation sites.”
Citations
Cites
Functional interaction of β-catenin with the transcription factor LEF-1
Behrens, J., von Kries, J. P., Kühl, M., Bruhn, L., Wedlich, D., Grosschedl, R., & Birchmeier, W. (1996) · Nature · doi:10.1038/382638a0 · Cited by 2,912
β‐catenin is a target for the ubiquitin–proteasome pathway
Aberle, H., Bauer, A., Stappert, J., Kispert, A., & Kemler, R. (1997) · The EMBO Journal · doi:10.1093/emboj/16.13.3797 · Cited by 2,586
Wnt signaling: a common theme in animal development
Cadigan, K. M., & Nusse, R. (1997) · Genes & Development · doi:10.1101/gad.11.24.3286 · Cited by 2,567
XTcf-3 Transcription Factor Mediates β-Catenin-Induced Axis Formation in Xenopus Embryos
Molenaar, M., van de Wetering, M., Oosterwegel, M., Peterson-Maduro, J., Godsave, S., Korinek, V., Roose, J., Destrée, O., & Clevers, H. (1996) · Cell · doi:10.1016/s0092-8674(00)80112-9 · Cited by 1,824
Wetering, M. L. V. D., Cavallo, R. A., Dooijes, D., van Beest, M., van Es, J. V., Loureiro, J., Ypma, A., Hursh, D., Jones, T. L., Bejsovec, A., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81925-x · Cited by 1,347
Regulation of transcription by MAP kinase cascades
Treisman, R. (1996) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(96)80067-6 · Cited by 1,296
Wnt Signaling in Oncogenesis and Embryogenesis--a Look Outside the Nucleus
Peifer, M., & Polakis, P. (2000) · Science · doi:10.1126/science.287.5458.1606 · Cited by 1,253
Ikeda, S., Kishida, S., Yamamoto, H., Murai, H., Koyama, S., & Kikuchi, A. (1998) · The EMBO Journal · doi:10.1093/emboj/17.5.1371 · Cited by 1,248
Drosophila Tcf and Groucho interact to repress Wingless signalling activity
Cavallo, R. A., Cox, R. T., Moline, M. M., Roose, J., Polevoy, G. A., Clevers, H., Peifer, M., & Bejsovec, A. (1998) · Nature · doi:10.1038/26982 · Cited by 730
Signal Transduction and the Control of Gene Expression
Brivanlou, A. H., & Darnell, J. E. (2002) · Science · doi:10.1126/science.1066355 · Cited by 699
Research works printed but not linked: 1
- Shin T. H., 1999, Cell, 4, 275
Cited by
Sorted by citations
The Wnt Signaling Pathway in Development and Disease
Logan, C. Y., & Nusse, R. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.010403.113126 · Cited by 5,325
“The phosphorylation of TCF/LEF by activated Nemo is thought to diminish the DNA-binding affinity of the β-catenin/TCF/LEF complex, thereby affecting transcriptional regulation of Wnt target genes (Ishitani et al. 1999, 2003).”
BackgroundWnt Signaling: Multiple Pathways, Multiple Receptors, and Multiple Transcription Factors
Gordon, M. D., & Nusse, R. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.r600015200 · Cited by 1,333
Purified Wnt5a Protein Activates or Inhibits β-Catenin–TCF Signaling Depending on Receptor Context
Mikels, A. J., & Nusse, R. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040115 · Cited by 1,244
“This phosphorylation of TCF/LEF prevents the b-catenin–TCF/LEF transcriptional complex from binding to DNA [17,18,36].”
BackgroundWnt signaling in osteoblasts and bone diseases
Westendorf, J. J., Kahler, R. A., & Schroeder, T. M. (2004) · Gene · doi:10.1016/j.gene.2004.06.044 · Cited by 820
Chong, Z. Z., Li, F., & Maiese, K. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.02.004 · Cited by 536
Metadata
- Authors
- Ishitani, T., Ninomiya-Tsuji, J., & Matsumoto, K.
- Affiliations
- Nagoya University (JP)
- Department of Molecular Biology, Graduate School of Science, Nagoya University, and CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya 464-8602, Japan
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2003-02-01
- Volume
- 23
- Issue
- 4
- Pages
- 1379-1389
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC141159
- OpenAlex
- W2113359377
- Semantic Scholar
- c5bd5fdc22c48d8a897ece5568678314f28893e2
- Cited by
- 212
- References
- 38
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 8 · 2016: 7 · 2015: 11 · 2014: 14 · 2013: 11 · 2012: 13
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- Core Research for Evolutional Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Keywords
- Nemo-like kinase, TCF4, Wnt/β-catenin signaling, β-catenin, transcriptional repression, MAPK signaling, TAK1, serine/threonine phosphorylation, transcriptional activity, protein-protein interaction
- MeSH terms
- MAP Kinase Kinase Kinase 7, Amino Acid Sequence, Cells, Cultured, Cytoskeletal Proteins, DNA-Binding Proteins, Humans, Molecular Sequence Data, Mutation, Phosphorylation, Proto-Oncogene Proteins, Serine, Threonine, Transcription Factors, Valine, Signal Transduction, Trans-Activators, Down-Regulation, Protein Serine-Threonine Kinases, Sequence Homology, Amino Acid, Amino Acid Substitution, Two-Hybrid System Techniques, Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinases, Zebrafish Proteins, Intracellular Signaling Peptides and Proteins, Wnt Proteins, beta Catenin, TCF Transcription Factors, Lymphoid Enhancer-Binding Factor 1, Transcription Factor 7-Like 2 Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-18, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
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Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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