The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index; 10 of the 28 sources its claims cite were checked for support.
DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1
Open accessAbstract
Cytokine-dependent gene transcription greatly depends on the tyrosine phosphorylation (“activation”) of Stat proteins at the cell membrane. This rapidly leads to their accumulation in the nucleus by an unknown mechanism. We performed microinjections of recombinant Stat1 protein to show that nuclear accumulation of phosphorylated Stat1 can occur without cytokine stimulation of cells. Microinjection of Stat1 antibody and treatment of cells with kinase or phosphatase inhibitors revealed that nuclear accumulation is a highly dynamic process sustained by Stat1 nucleocytoplasmic cycling and continuous kinase activity. By characterizing nuclear accumulation mutants, it is demonstrated that nuclear import and nuclear retention are two separate steps leading up to nuclear accumulation, with nonspecific DNA binding of activated Stat1 being sufficient for nuclear retention. Critical for nuclear buildup of Stat1 and the subsequent nuclear export is the point of time of tyrosine dephosphorylation, because our data indicate that activated Stat1 is incapable of leaving the nucleus and requires dephosphorylation to do so. It is demonstrated that the inactivation of Stat1 is controlled by its exchange reaction with DNA, whereby DNA binding protects Stat1 from dephosphorylation in a sequence-specific manner. Thus, during nuclear accumulation, a surprisingly simple mechanism integrates central aspects of cytokine-dependent gene regulation, for example, receptor monitoring, promoter occupancy, and transcription factor inactivation.
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Written from the paper’s full text.
TL;DR
This paper shows that tyrosine-phosphorylated Stat1 accumulates in the nucleus without cytokine receptor activation, and that nuclear accumulation is a dynamic process requiring continuous nucleocytoplasmic shuttling and kinase activity. DNA binding, especially nonspecific DNA binding, mediates nuclear retention and protects Stat1 from tyrosine dephosphorylation, thereby controlling the duration of nuclear accumulation.
Key findings
- Microinjected tyrosine-phosphorylated Stat1 accumulated in the nucleus of untreated HeLa and U3A cells, whereas unphosphorylated Stat1 distributed pancellularly after ∼30 min and did not accumulate even after 3 h. Nuclear export required dephosphorylation: after nuclear injection, tyrosine-phosphorylated Stat1 remained nuclear at 6 h, while unphosphorylated Stat1 became almost pancellular.
- Nuclear accumulation was dynamic: staurosporine caused complete Stat1 dephosphorylation after 60 min and collapse of nuclear accumulation, while vanadate/H₂O₂ suppressed dephosphorylation and extended accumulation. Cytoplasmic antibody injection depleted nuclear Stat1 in ∼30 min, but vanadate prevented this clearance, indicating continuous shuttling.
- DNA binding controlled nuclear retention and inactivation. Stat1dna minus failed to accumulate in the nucleus despite unaltered import, whereas Stat1dna plus accumulated and bound specific and nonspecific DNA with almost equal avidity. DNA protected Stat1 from TC45 dephosphorylation in a concentration- and sequence-dependent manner; GAS sites protected better than unrelated DNA.
- FRAP showed altered intranuclear mobility: after IFNγ, wild-type Stat1 recovery was ∼18.6 ± 3.2 sec, while Stat1dna plus was ∼206.7 ± 30.1 sec; with vanadate, wild-type was ∼46.4 ± 11.2 sec and dna plus ∼233.7 ± 46.6 sec. Stat1dna plus showed prolonged nuclear accumulation, Stat1dna off showed abbreviated accumulation, but neither dna plus nor dna minus induced a GAS-driven reporter in response to IFNγ.
Methods
- Recombinant human Stat1 variants were purified from baculovirus-infected Sf9 cells, in vitro tyrosine-phosphorylated, and microinjected into HeLa and U3A cells. Cells were treated with IFNγ, staurosporine, leptomycin B, and vanadate/H₂O₂; antibody microinjection was used to probe nucleocytoplasmic shuttling.
- DNA-binding mutants were generated by site-directed mutagenesis and analyzed by EMSA, biotinylated-oligonucleotide pull-down, coimmunoprecipitation, Western blotting, immunocytochemistry, and luciferase reporter assays.
- In vitro dephosphorylation used purified TC45 phosphatase with or without GAS or mutant DNA. Intranuclear mobility was measured by FRAP, and immunofluorescence intensities were quantified with Student’s t-test or ANOVA/Tukey tests.
Limitations
- The paper states no formal limitations section. It notes that nuclear dephosphorylation of recombinant Stat1 was slow compared with endogenous protein, which could be caused by the high concentration of injected material or by the absence of Arg31 methylation. It also notes that no data are available concerning nonspecific DNA binding of previously reported Stat1 mutants.
- Evident from the text: conclusions rely heavily on microinjection, overexpression, and purified in vitro systems, which may not fully reproduce endogenous chromatin and cellular contexts. FRAP sample sizes are small (n = 4–12 per condition), and mutant proteins could have effects beyond altered DNA binding.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
10 of 28 cited sources checked · 8 supported · 0 flagged · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Additionally, we included another DNA binding mutant, named Stat1dna off here, that was previ- ously characterized by Darnell and coworkers (Yang et al. 2002) and displays a markedly increased off-rate from GAS sites.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Stat1 DNA-binding mutants discriminate nuclear retention from nuclear import
What the sources say
- Supportedcites Yang et al. 2002 source
The Results report that STAT1(K544A/E545A) dissociates from DNA much faster than wild-type STAT1, with a mutant–DNA complex half-life at least 40 times shorter. The Discussion identifies a greatly accelerated off-rate at the IRF-1 and m67 sites; the paper describes these as GAS binding sites. “Stat1dna off” is the citing authors’ name for the mutant. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Quantitative analysis of the Stat1-DNA exchange reaction had revealed identical affinities for various sites, but despite having similar apparent K d values, the binding with DNA may differ significantly in rates of association with and dissociation from the Stat1 protein (Vinkemeier et al. 1996).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
What the sources say
- Supportedcites Vinkemeier et al. 1996 source
The Abstract (page not indicated in our copy) says the phosphorylated Stat1 preparations bound to various DNA recognition sites with the same reported equilibrium value. It also reports substantially different dissociation times for weak and strong sites, consistent with the citing sentence’s distinction between apparent affinity and binding kinetics. (LLM, conf=0.92)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“the cell line U3A (data not shown), which does not express Stat1 (Müller et al. 1993).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > The role of receptor activation and tyrosine phosphorylation in nucleocytoplasmic shuttling and nuclear accumulation of Stat1
What the sources say
- Supportedcites Müller et al. 1993 source
The Results passage (Introduction-labelled section; page unavailable) reports that U3A cells lacked the p91 and p84 polypeptides. The paper uses those names for the products of the p84/91 gene rather than the later name Stat1, but the reported lack of expression supports the claim. (LLM, conf=0.90)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Quantitative analysis of the Stat1-DNA exchange reaction had revealed identical affinities for various sites, but despite having similar apparent K d values, the binding with DNA may differ significantly in rates of association with and dissociation from the Stat1 protein (Vinkemeier et al. 1996).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
What the sources say
- Supportedcites Vinkemeier et al. 1996 source
The Abstract reports approximately the same equilibrium binding constant for various Stat1 DNA sites, but much faster dissociation from ‘weak’ than from ‘strong’ sites. This supports the claim that similar apparent affinities can mask differences in binding kinetics; the passage does not separately report association-rate measurements. (LLM, conf=0.85)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
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
“whereby DNA binding protects Stat1 from dephosphorylation in a sequence-specific manner.”
- Also stated in: § DNA-bound Stat1 is protected from tyrosine dephosphorylation · plain
“In conclusion, Stat1 that was not bound to DNA underwent tyrosine dephosphorylation at maximum rate, whereas DNA binding protected this molecule from inactivation in a sequence-dependent manner.”
- Also stated in: § Abstract · plain
“DNA-bound Stat1 is protected from dephosphorylation and is thus transiently retained in the nucleus.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § DNA-bound Stat1 is protected from tyrosine dephosphorylation · plain
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 performed microinjections of recombinant Stat1 protein to show that nuclear accumulation of phosphorylated Stat1 can occur without cytokine stimulation of cells.”
- Also stated in: § The role of receptor activation and tyrosine phosphorylation in nucleocytoplasmic shuttling and nuclear accumulation of Stat1 · boosted
“Notably, nuclear translocation and the subsequent accumulation of tyrosine-phosphorylated Stat1 were entirely independent of IFN stimulation or receptor activation.”
- Also stated in: § Discussion · boosted
“Nuclear translocation and accumulation of activated Stat1 can occur without receptor activation, as demonstrated by microinjection of in vitro phosphorylated protein (Fig. 1C).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Abstract
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Recombinant Stat1 protein purified from baculovirus-infected Sf9 cells and microinjected into cells is correctly folded and functionally equivalent to endogenous Stat1.
- Also stated in: § The role of receptor activation and tyrosine phosphorylation in nucleocytoplasmic shuttling and nuclear accumulation of Stat1 · boosted
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, opposite to Stat1wt, the protective influence of DNA had no sequence-specific component, as both the GAS-containing oligonucleotide and a nonspecific DNA were equally efficient in preventing Stat1 inactivation (Fig. 4C).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA-bound Stat1 is protected from tyrosine dephosphorylation
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: In vitro dephosphorylation of recombinant Stat1 by TC45 reflects the in vivo dephosphorylation and inactivation of Stat1.
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
“This situation was stable, and nuclear accumulation did not occur even after 3 h (data not shown).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > The role of receptor activation and tyrosine phosphorylation in nucleocytoplasmic shuttling and nuclear accumulation of Stat1
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Recombinant Stat1 protein purified from baculovirus-infected Sf9 cells and microinjected into cells is correctly folded and functionally equivalent to endogenous Stat1.
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 presence of DNA, however, the tyrosine dephosphorylation of Stat1 was strongly reduced in a concentrationdependent manner (Fig. 4A).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA-bound Stat1 is protected from tyrosine dephosphorylation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: In vitro dephosphorylation of recombinant Stat1 by TC45 reflects the in vivo dephosphorylation and inactivation of Stat1.
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 is shown in Table 1, in unstimulated cells, the Stat1 variants did not differ from one another because we determined almost identical recovery rates.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA binding determines the duration of nuclear accumulation
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 43
- Probably not a substantial claim. 14
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Compared with other studies, the mobility of Stat1 was much faster than the core histones and similar to other inducible transcriptional regulators (McNally et al. 2000; Kimura and Cook 2001; Lillemeier et al. 2001).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA binding determines the duration of nuclear accumulation
What the sources say
- Not checked — no full text of the sourcecites McNally et al. 2000 source
- Supportedcites Kimura and Cook 2001 source
Kimura and Cook support the core-histone side of this multi-citation comparison. Their Discussion ('Transcriptional Activity of the Different Populations'; page not provided) reports slow and essentially immobile histone populations, including H2B-GFP fractions with recovery half-times of about 130 minutes and over 510 minutes. The paper does not itself compare those rates with Stat1; the citation is being used for the histone measurements. (LLM, conf=0.86)
- Partly supportedcites Lillemeier et al. 2001 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) describes STAT1–GFP as highly mobile and compares its dynamic interactions with those of the glucocorticoid receptor, an inducible transcriptional regulator. It does not compare STAT1 mobility with that of core histones, so that part of the claim is not supported by this paper. (LLM, conf=0.84)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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
“Given that Stat1 has a slow turnover time (t 1/2 > 8 h; Lee et al. 1997) but dephosphorylation is rapid (t 1/2 < 15 min; Haspel et al. 1996), we wanted to determine how long Stat1 molecules remained nuclear.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Stat1 nuclear accumulation is a dynamic process sustained by continuous shuttling and kinase activity
What the sources say
- Not checked — no full text of the sourcecites Lee et al. 1997 source
- Supportedcites Haspel et al. 1996 source
The section “Direct evidence for cytoplasmic-nuclear cycling of Stat1 involving a tyrosine phosphatase” estimates the half-life of phosphorylated nuclear Stat1 at at most 15 minutes. The Abstract attributes removal of activated Stat1 to a protein tyrosine phosphatase. The turnover-time claim is cited to Lee et al., not to this paper. (LLM, conf=0.91)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“This observation extends the previous finding that dimerization is sufficient for nuclear import of activated Stat1 (Milocco et al. 1999).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
What the sources say
- Supportedcites Milocco et al. 1999 source
The Discussion states that dimerization alone is sufficient to unmask Stat1’s nuclear localization sequence and activate nuclear translocation. The Abstract reports the same conclusion, based on experiments with a Stat1–ER chimera. The supplied passages do not give page numbers. (LLM, conf=0.94)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The analysis of nucleocytoplasmic transport of Stat1 has revealed its high, energy-independent mobility in the cytoplasm, which is indicative of random diffusion (Lillemeier et al. 2001).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > The role of receptor activation and tyrosine phosphorylation in nucleocytoplasmic shuttling and nuclear accumulation of Stat1
What the sources say
- Supportedcites Lillemeier et al. 2001 source
The Discussion reports that cytoplasmic STAT1–GFP moves rapidly, comparably to freely diffusible GFP, and independently of ATP. The FRAP results also show similar cytoplasmic recovery rates with and without ATP depletion, supporting the inference of random diffusion. (LLM, conf=0.94)
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“purified TC-PTPa (also called TC45; Ibarra-Sanchez et al. 2000), a ubiquitously expressed Stat1-specific nuclear tyrosine phosphatase (ten Hoeve et al. 2002).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA-bound Stat1 is protected from tyrosine dephosphorylation
What the sources say
- Not checked — no full text of the sourcecites Ibarra-Sanchez et al. 2000 source
- Partly supportedcites ten Hoeve et al. 2002 sourceExperimental — accuracy not yet measured
The Results identify TC45 as a mainly nuclear phosphatase that dephosphorylates Stat1. But the Discussion says the TC-PTP gene is ubiquitously expressed—not specifically that TC45 is—and the Results and Discussion also implicate TC45 in Stat3 dephosphorylation, so “Stat1-specific” overstates its selectivity. Page numbers were not available in our copy. (LLM, conf=0.88)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
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
“Notably, fluorescence recovery of all Stat1 variant proteins was complete even in the absence of phosphatase activity, and the mobility continued to differ between the DNA binding mutants (Fig. 5B).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA binding determines the duration of nuclear accumulation
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“On the contrary, inactivating tyrosine phosphatases by treatment of cells with pervanadate (Gordon 1991) not only suppressed Stat1 dephosphorylation but also extended the duration of nuclear accumulation (Fig. 2A,B, bottom panels).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Stat1 nuclear accumulation is a dynamic process sustained by continuous shuttling and kinase activity
What the sources say
- Not checked — no full text of the sourcecites Gordon 1991 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“Strikingly, preventing tyrosine dephosphorylation had little impact on the intranuclear mobility of all Stat1 proteins investigated (Fig. 5B), because recovery times increased only by a factor of 2.5 or less (Table 1).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA binding determines the duration of nuclear accumulation
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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, Stat1dna plus was much less sensitive to the cessation of kinase activity, as the level of activated protein remained high, indicating strongly reduced tyrosine dephosphorylation (Fig. 5A).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA binding determines the duration of nuclear accumulation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“This resulted in the complete dephosphorylation of Stat1 after 60 min and a collapse of nuclear accumulation that closely mirrored the kinetics of tyrosine dephosphorylation (Fig. 2A,B, top panels).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Stat1 nuclear accumulation is a dynamic process sustained by continuous shuttling and kinase activity
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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 Stat1 protein entered the nucleus rapidly and showed a pancellular distribution after ∼30 min (Fig. 1B).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > The role of receptor activation and tyrosine phosphorylation in nucleocytoplasmic shuttling and nuclear accumulation of Stat1
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Recombinant Stat1 protein purified from baculovirus-infected Sf9 cells and microinjected into cells is correctly folded and functionally equivalent to endogenous Stat1.
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
“Remarkably, the mutant Stat1dna plus showed a significantly reduced intranuclear mobility, and the recovery time was extended to ∼200 sec.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA binding determines the duration of nuclear accumulation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“These data confirm that unphosphorylated Stat1 is capable of nucleocytoplasmic shuttling, yet accumulation only occurred with the tyrosine-phosphorylated species.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > The role of receptor activation and tyrosine phosphorylation in nucleocytoplasmic shuttling and nuclear accumulation of Stat1
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Recombinant Stat1 protein purified from baculovirus-infected Sf9 cells and microinjected into cells is correctly folded and functionally equivalent to endogenous Stat1.
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 is shown in Figure 5A, the initial concentrations of activated Stats were similar for all variants after 30 min of IFN␥ treatment, indicating their comparable facility to become tyrosine-phosphorylated.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA binding determines the duration of nuclear accumulation
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“Importantly, fluorescence recovery was complete for all Stat1 variants, indicating that no immobile population was present within the nucleus during accumulation.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA binding determines the duration of nuclear accumulation
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“Importantly, the antibody-induced nuclear accumulation of Stat1wt and Stat1dna minus could not be discriminated, thus indicating unperturbed import of the mutant.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Stat1 DNA-binding mutants discriminate nuclear retention from nuclear import
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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 Stat1 variants were expressed well and phosphorylated on tyrosine 701 in response to IFN␥ (Fig. 3B).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Stat1 DNA-binding mutants discriminate nuclear retention from nuclear import
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“Addition of a negative charge in position 327 (Thr to Glu) of Stat1dna minus also resulted in defective nuclear accumulation, albeit less severely, because a partial accumulation could still be induced by IFN␥ (data not shown).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Stat1 DNA-binding mutants discriminate nuclear retention from nuclear import
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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, treatment of cells with the tyrosine phosphatase inhibitor vanadate precluded the antibody-induced nuclear clearance of Stat1, because even after 90 min of incubation there was no translocation of Stat1 to the cytoplasm (Fig. 2C, sec-ond row).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Stat1 nuclear accumulation is a dynamic process sustained by continuous shuttling and kinase activity
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“Wild-type Stat1 was highly mobile in the nucleus, as were the dna off and dna minus mutants.These proteins had recovery times of ∼20 sec (Fig. 5B).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA binding determines the duration of nuclear accumulation
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“First, we observed the nucleocytoplasmic distribution of GFP-fusion proteins before and after IFN␥ stimulation and found accumulation of Stat1dna plus and dna off , whereas the Stat1dna minus mutant failed to accumulate in the nucleus in response to IFN␥ (Fig. 3C).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Stat1 DNA-binding mutants discriminate nuclear retention from nuclear import
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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, after 6 h, considerable amounts of Stat1 were found outside of the nucleus, because an almost pancellular distribution was observed with a Stat1-specific antibody (Fig. 1D,F).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > The role of receptor activation and tyrosine phosphorylation in nucleocytoplasmic shuttling and nuclear accumulation of Stat1
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Recombinant Stat1 protein purified from baculovirus-infected Sf9 cells and microinjected into cells is correctly folded and functionally equivalent to endogenous Stat1.
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
“Figure 5 demonstrates that nuclear accumu- lation of Stat1dna off is shortened, despite the fact that this mutant was activated to a similar extent as wildtype Stat1 and despite its normal ability to recognize GAS sites (Fig. 3D).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“Nonetheless, because tyrosine-phosphorylated Stat1 was not exported readily but was retained in the nucleus, DNA binding per se cannot account for nuclear retention.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“Judged by several criteria, such as the abundance of phosphorylated Stat1 in nuclear extracts, the antibody-induced nuclear precipitation after IFN␥ stimulation, and the rapid nuclear accumulation induced by an export block through preventing tyrosine dephosphorylation (Fig. 3), the IFN␥-induced nuclear import of Stat1dna minus proceeded unaltered, but nevertheless the mutant was incapable of nuc”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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 nuclear export of wild-type Stat1 was blocked after stimulation with IFN␥ in the presence of vanadate, whereas nuclear export of both a Stat1 variant with a mutated tyrosine phosphorylation site and an export reporter construct were not affected by this treatment (Fig. 2C).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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 Stat1 protein achieves equilibrium in DNA binding very rapidly (Ӷ30 sec); however, although the protein-DNA complex had a half-life of no more than 3 min for any of the GAS sites investigated, the off-times varied at least sixfold.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“Nevertheless, the cycling rate was high, as cytoplasmic trapping depleted nuclear Stat1 in ∼30 min (Fig. 2C), and blocking of kinase activity led to a collapse of nuclear accumulation in <60 min (Fig. 2B).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“This was exemplified by the opposed nuclear accumulation abilities of Stat1dna minus and dna plus , neither of which could discriminate GAS elements from nonspecific sites, although they differed from one another in their overall DNA affinity.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“because our data indicate that activated Stat1 is incapable of leaving the nucleus and requires dephosphorylation to do so.”
- Also stated in: § The role of receptor activation and tyrosine phosphorylation in nucleocytoplasmic shuttling and nuclear accumulation of Stat1 · plain
“Conversely, nuclear export required dephosphorylation.”
- Also stated in: § Discussion · plain
“We conclude that tyrosinephosphorylated dimers were incapable of nucleocytoplasmic shuttling and required inactivation before release into the cytoplasm.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § The role of receptor activation and tyrosine phosphorylation in nucleocytoplasmic shuttling and nuclear accumulation of Stat1 · 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
“Thus, Stat1dna plus bound to DNA, albeit nonspecifically, whereas dna minus did not.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Stat1 DNA-binding mutants discriminate nuclear retention from nuclear import
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“In conclusion, Stat1 that was not bound to DNA underwent tyrosine dephosphorylation at maximum rate, whereas DNA binding protected this molecule from inactivation in a sequence-dependent manner.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA-bound Stat1 is protected from tyrosine dephosphorylation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: In vitro dephosphorylation of recombinant Stat1 by TC45 reflects the in vivo dephosphorylation and inactivation of Stat1.
None of the sources cited for this claim have been checked yet.
In the paper
“Nuclear accumulation was shown to depend on the integrity of the DNA-binding domain, which can be attributed to the need for a functional dsNLS located here (Fagerlund et al. 2002;Meyer et al. 2002a).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Stat1 DNA-binding mutants discriminate nuclear retention from nuclear import
What the sources say
- Not checked — no full text of the sourcecites Fagerlund et al. 2002 source
- Not matchedcites Meyer et al. 2002a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Thus, DNA binding differences were reflected in an altered mobility in the nuclear compartment, with enhanced binding correlating with reduced mobility.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA binding determines the duration of nuclear accumulation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Thus, although the enzymatic reaction was required for nuclear export, it could not be the causative step for the release of Stat1 from its nuclear DNA tether.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“These data describe a mechanism that allows nuclear Stats to monitor receptor activity and that at the same time selectively promotes occupation of target regulatory elements.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“We also point out the fact that GAS sites are generally poorly conserved, making it difficult to predict actual chromatin binding sites (Decker et al. 1997), indicating that the distinction between”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
What the sources say
- Not checked — no full text of the sourcecites Decker et al. 1997 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Thus, nuclear import does not necessarily result in nuclear accumulation, which is only observed with tyrosine-phosphorylated Stat1 dimers containing a functional SH2 domain (Mowen and David 1998).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Abstract
What the sources say
- Not checked — no full text of the sourcecites Mowen and David 1998 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The two preparations differed in their Stat1 dephosphorylation activity, but the specificity of the reaction was unchanged by the truncation (data not shown).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA-bound Stat1 is protected from tyrosine dephosphorylation
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“We show that nonspecific interactions with DNA are observable for wild-type Stat1 (Fig. 3E), and binding to DNA outside of consensus binding elements is common for transcriptional regulators (Lin and Riggs 1975).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
What the sources say
- Not checked — no full text of the sourcecites Lin and Riggs 1975 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This variant enzyme was demonstrated to exhibit increased phosphatase activity (Hao et al. 1997).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > DNA-bound Stat1 is protected from tyrosine dephosphorylation
What the sources say
- Not checked — no full text of the sourcecites Hao et al. 1997 source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Binding to the glucocorticoid receptor enhanced DNA binding of Stat5, which correlated with its prolonged tyrosine phosphorylation in vivo (Wyszomierski et al. 1999).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
What the sources say
- Not checked — no full text of the sourcecites Wyszomierski et al. 1999 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“For these reasons, DNA binding is sufficient but not necessary for nuclear accumulation.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Fast dephosphorylation with concomitant nuclear export and reactivation in the cytoplasm are both essential for dynamic signaling.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“A negative influence of DNA binding on Stat dephosphorylation was noted earlier also for Stat5.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
What the sources say
- Not checked — no full text of the sourcecites Wyszomierski et al. 1999 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“We conclude that tyrosinephosphorylated dimers were incapable of nucleocytoplasmic shuttling and required inactivation before release into the cytoplasm.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“A model is shown in Figure 7 that explains the molecular basis of the signaldependent nuclear accumulation of the transcription factor Stat1 and outlines the constitutive cycling of Stat1 both in resting cells and during stimulation with IFN␥.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“This way, the process of nuclear accumulation might confer a selection advantage on Stat1 dimers bound to GAS consensus promoter sites.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Homogeneous tyrosine phosphorylation of the final preparation was verified by MALDI analysis, as was the absence of Arg 31 methylation.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Purification and microinjection of recombinant Stat1
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“As expected, full-length and truncated TC45 dephosphorylated pNPP with identical rates (Hao et al. 1997).”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Dephosphorylation assays
What the sources say
- Not checked — no full text of the sourcecites Hao et al. 1997 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Dephosphorylation of the control substrate p-nitrophenyl phosphate (pNPP) was not influenced by DNA (25 nM GAS; data not shown)”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > Dephosphorylation assays
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Mutations were verified by DNA sequencing.”
§ DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 > cDNAs, cell culture, and reagents
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Recombinant Stat1 protein purified from baculovirus-infected Sf9 cells and microinjected into cells is correctly folded and functionally equivalent to endogenous Stat1.
“To investigate nuclear translocation, we purified the human Stat1 protein from baculovirus-infected Sf9 cells (Fig. 1A).”
“These proteins were microinjected into HeLa cells and the cell line U3A (data not shown), which does not express Stat1 (Müller et al. 1993).”
The paper relies on this without support.
In vitro dephosphorylation of recombinant Stat1 by TC45 reflects the in vivo dephosphorylation and inactivation of Stat1.
“At first we therefore examined the influence of DNA binding on the dephosphorylation of Stat1 variants in vitro.”
“In conjunction with the in vitro dephosphorylation data, we conclude that the release of Stat1 from DNA did not require enzymatic activity.”
Citations
Cites
Darnell, J. E., Kerr, L. M., & Stark, G. R. (1994) · Science · doi:10.1126/science.8197455 · Cited by 6,080
Darnell, J. E. (1997) · Science · doi:10.1126/science.277.5332.1630 · Cited by 3,979
Mobility measurement by analysis of fluorescence photobleaching recovery kinetics
Axelrod, D., Koppel, D. E., Schlessinger, J., Elson, E. L., & Webb, W. W. (1976) · Biophysical Journal · doi:10.1016/s0006-3495(76)85755-4 · Cited by 2,717
Signaling through the JAK/STAT pathway, recent advances and future challenges
Kisseleva, T., Bhattacharya, S., Braunstein, J., & Schindler, C. (2002) · Gene · doi:10.1016/s0378-1119(02)00398-0 · Cited by 1,167
Leptomycin B Inhibition of Signal-Mediated Nuclear Export by Direct Binding to CRM1
Kudo, N. R., Wolff, B., Sekimoto, T., Schreiner, E. P., Yoneda, Y., Yanagida, M., Horinouchi, S., & Yoshida, M. (1998) · Experimental Cell Research · doi:10.1006/excr.1998.4136 · Cited by 812 · cited 2×
“When we additionally included leptomycin B, an inhibitor of the export receptor CRM1 (Kudo et al. 1998), the rapid termination of nuclear accumulation was not pre- GENES & DEVELOPMENT 1993 vented, confirming CRM1-independent nuclear export (Begitt et al. 2000; data not shown).”
BackgroundShuai, K., Horvath, C. M., Huang, L. H. T., Qureshi, S. A., Cowburn, D., & Darnell, J. E. (1994) · Cell · doi:10.1016/0092-8674(94)90357-3 · Cited by 807 · cited 2×
“Stat1 monomers form high-avidity reciprocal homo- or heterodimers and detach from their receptor docking site after phosphorylation of tyrosine residue 701 at their C terminus (Shuai et al. 1993, 1994; Greenlund et al. 1995).”
BackgroundA Single Phosphotyrosine Residue of Stat91 Required for Gene Activation by Interferon-γ
Shuai, K., Stark, G. R., Kerr, L. M., & Darnell, J. E. (1993) · Science · doi:10.1126/science.7690989 · Cited by 802 · cited 2×
“Stat1 monomers form high-avidity reciprocal homo- or heterodimers and detach from their receptor docking site after phosphorylation of tyrosine residue 701 at their C terminus (Shuai et al. 1993, 1994; Greenlund et al. 1995).”
BackgroundMethodThe glucocorticoid receptor: rapid exchange with regulatory sites in living cells
McNally, J. G., Müller, W. G., Walker, D., Wolford, R., & Hager, G. L. (2000) · Science · doi:10.1126/science.287.5456.1262 · Cited by 802
Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein.
Shuai, K., Schindler, C., Prezioso, V., & Darnell, J. (1992) · Science · doi:10.1126/science.1281555 · Cited by 784 · cited 2×
“Stat1 monomers form high-avidity reciprocal homo- or heterodimers and detach from their receptor docking site after phosphorylation of tyrosine residue 701 at their C terminus (Shuai et al. 1993, 1994; Greenlund et al. 1995).”
BackgroundMethodCrystal Structure of a Tyrosine Phosphorylated STAT-1 Dimer Bound to DNA
Chen, X., Vinkemeier, U., Zhao, Y., Jeruzalmi, D., Darnell, J. E., Jr., & Kuriyan, J. (1998) · Cell · doi:10.1016/s0092-8674(00)81443-9 · Cited by 734 · cited 1×
“Guided by the Stat1–DNA cocrystal structure (Chen et al. 1998), we mutated residues in the DNAbinding domain that potentially make backbone contacts with phosphate groups in the DNA and are not part of the dsNLS (Fig.”
MethodSelf-citation
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Items 101–161 of 161
Promoter Occupancy of STAT1 in Interferon Responses Is Regulated by Processive Transcription
Wiesauer, I., Gaumannmüller, C., Steinparzer, I., Strobl, B., & Kovarik, P. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.01097-14 · Cited by 16
STAT1: A many-sided transcription factor
Kostanyan, I. A., Vonarshenko, A. V., & Липкин, В. М. (2010) · Russian Journal of Bioorganic Chemistry · doi:10.1134/s1068162010010024 · Cited by 15
Dissecting functions of the N-terminal domain and GAS-site recognition in STAT3 nuclear trafficking
Martincuks, A., Fahrenkamp, D., Haan, S., Herrmann, A., Küster, A., & Müller‐Newen, G. (2016) · Cellular Signalling · doi:10.1016/j.cellsig.2016.03.011 · Cited by 16
“The same observation has been made for IFNγinduced STAT1 signaling [51].”
BackgroundKoch, V., Staab, J., Ruppert, V., & Meyer, T. (2012) · BMC Cell Biology · doi:10.1186/1471-2121-13-22 · Cited by 15
“STAT1 mutants with impaired nuclear import are exposed to the high kinase activity and comparably low phosphatase activity in the cytosol [33], and a DNA-binding mutant termed STAT1-dna has been described, which failed to recognize GAS probes in gelshift assays [40].”
BackgroundSelf-citationJAK-STAT Signaling Circuits in Myocarditis and Dilated Cardiomyopathy*
Ruppert, V., & Meyer, T. (2007) · Herz · doi:10.1007/s00059-007-3040-x · Cited by 13
“Within the nucleus, STAT dimers bind to specific DNA elements of the consensus sequence 5'-TT(N4–6)AA-'3, termed gamma-activated sites (GAS), in the promoters of target genes and modulate gene transcription [26].”
BackgroundInfluentialSelf-citationModel-based extension of high-throughput to high-content data
Pfeifer, A. C., Kaschek, D., Bachmann, J., et al. (2010) · BMC Systems Biology · doi:10.1186/1752-0509-4-106 · Cited by 12
“It has been proposed that import of STAT is enhanced upon activation [16], while export of activated STAT is slowed down either through retention in the nucleus by DNA binding [17] or possibly a different export mechanism [15].”
BackgroundActivation of the transcription factor NFAT1: concerted or modular regulation?
Salazar, C., & Höfer, T. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.12.029 · Cited by 12
“Here, DNA binding protects Stat1 from a dephosphorylation that would abolish its DNA affinity [15].”
BackgroundPelzel, C., Begitt, A., Wenta, N., & Vinkemeier, U. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.02.024 · Cited by 11
“In the cell nucleus, STAT1 inactivation is ultimately limited by the kinetics of DNA binding, whereby STAT1 is available for dephosphorylation only in its DNA unbound state (Meyer et al., 2003).”
BackgroundSelf-citationSTAT module can function as a biphasic amplitude filter
Mayya, V., & Loew, L. M. (2005) · Systems Biology · doi:10.1049/sb:20045037 · Cited by 11
An inhibitory effect on the nuclear accumulation of phospho-STAT1 by its unphosphorylated form
Menon, P. R., Staab, J., Gregus, A., et al. (2022) · Cell Communication and Signaling · doi:10.1186/s12964-022-00841-3 · Cited by 10
“To this end, two point-mutations, namely V426D/T427D, which have been previously characterised as DNAminus for markedly reducing affinity to DNA, were introduced in the R602L/Y701F-GFP construct [25].”
BackgroundSelf-citationRivera, L., Kraiselburd, E., & Meléndez, L. M. (2016) · Journal of NeuroVirology · doi:10.1007/s13365-016-0443-6 · Cited by 10
“Other studies reported that STAT-1 dimers do not require to be stimulated by cytokines such as IFN-β to move in and be stored in the nucleus (Meyer et al. 2003).”
BackgroundPhosphorylation on Ser106 Modulates the Cellular Functions of the SHOX Homeodomain Protein
Marchini, A., Daeffler, L., Marttila, T., et al. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.11.007 · Cited by 10
Leanza, E. C., Hoshida, M. S., Costa, A. F., et al. (2007) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2007.00537.x · Cited by 8
Marg, A., Meyer, T., Vigneron, M., & Vinkemeier, U. (2008) · Cytometry Part A · doi:10.1002/cyto.a.20635 · Cited by 8
“06 in antibody-injected cells (n 5 12 cells in each group) (33).”
BackgroundSelf-citationStaab, J., Riebeling, T., Koch, V., Herrmann‐Lingen, C., & Meyer, T. (2015) · Molecular Immunology · doi:10.1016/j.molimm.2015.07.015 · Cited by 7
Self-citationAntiviral activity of oligomerization-deficient Stat1.
Vinkemeier, U., & Meyer, T. (2005) · PubMed · Cited by 7
Self-citationStaab, J., Herrmann‐Lingen, C., & Meyer, T. (2013) · JAK-STAT · doi:10.4161/jkst.23576 · Cited by 7
Self-citationMethodologies for Measuring Protein Trafficking across Cellular Membranes
Lyu, Z., & Genereux, J. C. (2021) · ChemPlusChem · doi:10.1002/cplu.202100304 · Cited by 5
Riebeling, T., Staab, J., Herrmann‐Lingen, C., & Meyer, T. (2014) · BMC Biochemistry · doi:10.1186/s12858-014-0028-z · Cited by 5
“It is wellestablished that the antiparallel STAT1 dimer is the accessible substrate for the nuclear tyrosine phosphatase, while conversely DNA-binding protects parallel phosphodimers from being tyrosine dephosphorylated [18,22].”
BackgroundSelf-citationTumor Necrosis Factor alpha (TNFα) regulates CD40 expression through SMAR1 phosphorylation
Singh, K., Sinha, S., Malonia, S. K., & Chattopadhyay, S. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.12.055 · Cited by 6
Nast, R., Staab, J., Meyer, T., & Lüder, C. G. K. (2018) · Cellular Microbiology · doi:10.1111/cmi.12887 · Cited by 5
“Because nuclear export of STAT1 requires its dissociation from DNA (Meyer et al., 2003), it is in line with our observation of an increased affinity of STAT1 from parasite‐infected cells to GAS and non‐GAS DNA elements (see above).”
BackgroundSelf-citationMenon, P. R., Doudin, A., Gregus, A., Wirths, O., Staab, J., & Meyer, T. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.119118 · Cited by 6
Self-citationGene Activation by the Cytokine-Driven Transcription Factor STAT1
Nast, R., Staab, J., & Meyer, T. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.82699 · Cited by 4
“A STAT1 mutant termed STAT1 DNA, in which negative charges were introduced by substituting aspartic acid (Asp) for valine (Val) at position 426 (Val(426)Asp) and threonine at position 427 (Thr(427)Asp), was normally tyrosine phosphorylated in response to IFN-γ but essentially lost its DNA-binding activity [27].”
BackgroundInfluentialSelf-citationWilliams, R. J., Karpuzoglu, E., Connell, H., et al. (2019) · Journal of Toxicology and Environmental Health · doi:10.1080/15287394.2019.1591315 · Cited by 4
Use of fluorescence photobleaching techniques to measure the kinetics of intracellular transport
Davies, R. G., Jans, D. A., & Wagstaff, K. M. (2010) · Cited by 4
Doudin, A., Riebeling, T., Staab, J., et al. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.975012 · Cited by 3
“Active STATs are retained in the nucleus, only to return to the cytosol upon dephosphorylation by nuclear phosphatases, where they are rephosporylated at active receptors and participate in an additional round of nucleocytoplasmic translocation (10).”
BackgroundSelf-citationAssessing Sequence-Specific DNA Binding and Transcriptional Activity of STAT1 Transcription Factor
Meyer, T., & Vinkemeier, U. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-738-9_8 · Cited by 3
Self-citationHan, F., Luo, Y., Ge, N., & Xu, J. (2008) · Acta Biochimica et Biophysica Sinica · doi:10.1111/j.1745-7270.2008.00480.x · Cited by 2
Self-association of STAT Proteins from Monomers to Paracrystals
Droescher, M., & Vinkemeier, U. (2012) · Springer eBooks · doi:10.1007/978-3-7091-0891-8_4 · Cited by 2
Self-citationVitamin D Receptor and Retinoid X Receptor Subcellular Trafficking
Bársony, J. (2005) · Elsevier eBooks · doi:10.1016/b978-012252687-9/50025-5 · Cited by 1
Staab, J., Schwämmle, T., & Meyer, T. (2020) · Molecular Immunology · doi:10.1016/j.molimm.2020.10.005 · Cited by 1
Self-citationCellular responses mediated by the transcription factor STAT1 in murine inflammatory diseases
Riebeling, T. (2017) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-6074 · Cited by 1
Charakterisierung von Punktmutanten in der Linker-Domäne des humanen STAT1-Proteins
Grebe, J. (2016) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-5750 · Cited by 1
Bolten, J. C. (2013) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-4113 · Cited by 1
Molekulare Determinanten zur sequenzspezifischen DNA-Bindung des Transkriptionsfaktors STAT1
Hüntelmann, B. (2018) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-6655 · Cited by 1
Cytokine Signaling in Tissue Engineering
Meyer, T., Ruppert, V., & Maisch, B. (2009) · Springer eBooks · doi:10.1007/978-3-540-77755-7_7
Self-citationLebensqualität bei Melanom- Patienten unter adjuvanter Interferon- alpha 2a- Therapie
Rötzer, S. (2008) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-17787
VDR and RXR Subcellular Trafficking
Bársony, J. (2010) · Humana Press eBooks · doi:10.1007/978-1-60327-303-9_6
“Other well-characterized examples for signal-specific control of transcription factor localization are NF-κB (12), MAP kinases (13) ,S TAT ( 14 ) ,S mad1(15), and p53 (16, 17).”
BackgroundBarry, S. P. (2009) · UCL Discovery (University College London)
Gorina, R. (2008) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona)
DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF POTENTIAL STAT3 INHIBITORS AS ANTICANCER AGENTS
Masciocchi, D. (2012) · Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) · doi:10.13130/masciocchi-daniela_phd2012-02-13
Transcription Factors in Amphioxus
Yuan, S., Zhang, J., Zheng, T., et al. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-849903-0.00006-3
Modeling the Dynamics of the Immune Response
Abad, E. M., Villoslada, P., & García‐Ojalvo, J. (2017) · Systems Biology · doi:10.1002/9783527696130.ch10
Martincuks, A. (2017) · RWTH Publications (RWTH Aachen) · doi:10.18154/rwth-2017-01944
“The same observation has been made for IFNγ-induced STAT1 signaling [201].”
BackgroundDie Bedeutung der Coiled-coil-Domäne für die Inaktivierung des Transkriptionsfaktors STAT1
Petersen, J. (2020) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-7960
Schiffmann, J. C. (2020) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-8014
Menon, P. R. (2021) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-8488
Signal Pathways from the Plasma Membrane to the Nucleus Regulating Craniofacial Pattern Formation
Meyer, T. (2021) · Springer eBooks · doi:10.1007/978-3-030-46024-2_3
Self-citationFaculty Opinions recommendation of A phosphorylation-acetylation switch regulates STAT1 signaling.
Sharrocks, A. D. (2009) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1147405.604579
Reevaluation der potenziell onkogenen, Lymphom-assoziierten Missense-Mutation D427H im STAT3-Molekül
Behrendsen, L. S. (2023) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-9644
Bohne, N. M. (2023) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-9923
Sharma, A., Kaur, S., Arora, J. S., et al. (2024) · Journal of Dairy Research · doi:10.1017/s0022029924000530
“These get their name as transcription factors as they allow the proteins to control turning on and off these genes by attaching to the regulatory regions, (Meyer et al ., 2003).”
Xiao, J., & Qiu, J. (2025) · Journal of Interferon & Cytokine Research · doi:10.1177/10799907251389756
“After activation, STAT1 is dephosphorylated in the nucleus and translocated back to the cytoplasm, where it exists as either a monomer or an unphosphorylated dimer (Boisson-Dupuis et al., 2012; Haspel et al., 2002; Mertens et al., 2006; Meyer et al., 2003).”
Meyer, T., Lamprecht, F., Begitt, A., Höfer, T., & Vinkemeier, U. (2026) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2026.195151
Self-citationCytokine-induced nuclear translocation of STAT1 via a non-transferable NLSPreprint
Kumar, P., Cavey, J. R., Yang, R., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.28.754937
Self-citationZadeh, T. G. C. (2014) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-4775
Nouveaux rôles anti-tumoraux de STAT1 : expression des immunoglobulines et réparation de l'ADN
Lemadre, E. (2014) · doi:10.70675/20f9a9b0za689z421azad37z21caa1083b20
“La déphosphorylation de la Y701 de STAT1 est un processus rapide intervenant dans les trente minutes suivant l’activation cellulaire et est requise pour l’export du noyau (Meyer et al., 2003) (figure 9).”
Background
Metadata
- Authors
- Meyer, T., Marg, A., Lemke, P., Wiesner, B., & Vinkemeier, U.
- Affiliations
- Leibniz-Forschungsinstitut für Molekulare Pharmakologie (DE)
- Corresponding author
- Vinkemeier, Uwe
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2003-08-15
- Volume
- 17
- Issue
- 16
- Pages
- 1992-2005
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC196254
- OpenAlex
- W2099132542
- Semantic Scholar
- 229b280fb881046a1375087eb563a61164547ec3
- Cited by
- 161
- References
- 48
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 4 · 2014: 9 · 2013: 9 · 2012: 7
- Type
- posted content
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- Israel Cancer Research Fund
- Bundesministerium für Bildung und Forschung
- Université de Strasbourg
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- STAT1, DNA binding, tyrosine phosphorylation, tyrosine dephosphorylation, nucleocytoplasmic shuttling, nuclear import, nuclear retention, nuclear export, transcription factor inactivation, sequence-specific DNA binding, phosphatase activity
- MeSH terms
- Antibodies, Monoclonal, Cell Nucleus, Cytoplasm, DNA, DNA-Binding Proteins, Enzyme Inhibitors, HeLa Cells, Humans, Interferon-gamma, Models, Biological, Mutation, Phosphorylation, Recombinant Proteins, Transcription, Genetic, Tumor Cells, Cultured, Tyrosine, Vanadates, Transcriptional Activation, Trans-Activators, Active Transport, Cell Nucleus, STAT1 Transcription Factor
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