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
Flagged first, then by citations
Cited by
Sorted by citations
Regulation of JAK–STAT signalling in the immune system
Shuai, K., & Liu, B. (2003) · Nature reviews. Immunology · doi:10.1038/nri1226 · Cited by 1,409
“Recently, it has been shown that tyrosine phosphorylated STAT1 needs to be dephosphorylated to leave the nucleus, indicating a role for tyrosine phosphorylation in the nuclear retention of STAT1 (Ref”
BackgroundBiology and significance of the JAK/STAT signalling pathways
Kiu, H., & Nicholson, S. E. (2012) · Growth Factors · doi:10.3109/08977194.2012.660936 · Cited by 470
“…export factor, chromosome region maintenance 1 (Haspel et al. 1996; Begitt et al. 2000; McBride et al. 2000; MowenandDavid2000;Zenget al. 2002;Bhattacharya and Schindler 2003; Meyer et al. 2003; Banninger and Reich 2004; Marg et al. 2004); thus completing the activation and deactivation cycle.”
Sekrecka, A., Błaszczyk, K., Wesoły, J., & Bluyssen, H. A. R. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01135 · Cited by 333
“iFn independent IFN independent, basal expression of some ISGs has recently been linked to the nuclear localization of U-ISGF3 and U-GAF (56, 57).”
BackgroundInfluentialTranscriptional regulation by STAT1 and STAT2 in the interferon JAK-STAT pathway
Au-Yeung, N., Mandhana, R., & Horvath, C. M. (2013) · JAK-STAT · doi:10.4161/jkst.23931 · Cited by 307
“While the exact mechanism of nuclear retention of tyrosine phosphorylated STATs is not completely understood, dephosphorylation is required for STAT1 nuclear export in the type II IFN pathway.(26,27) Since STAT2, like STAT1, is exported from the nucleus by the CRM1 exportin, it is possible that a similar dephosphoryla…”
BackgroundBoisson‐Dupuis, S., Kong, X., Okada, S., Cypowyj, S., Puel, A., Abel, L., & Casanova, J. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.04.011 · Cited by 293
A phosphorylation-acetylation switch regulates STAT1 signalingPreprint
Krämer, O. H., Knauer, S. K., Greiner, G., Jandt, E., Reichardt, S., Gührs, K., Stauber, R. H., Böhmer, F., & Heinzel, T. (2009) · Genes & Development · doi:10.1101/gad.479209 · Cited by 282
“STAT1 DNA-binding mutants do not accumulate in the nucleus because of their rapid export via a leptomycin B (LMB)-sensitive CRM1-dependent mechanism (Meyer et al. 2003).”
BackgroundMethodInfluentialSTAT1 as a key modulator of cell death
Kim, H. S., & Lee, M. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2006.09.003 · Cited by 283
Williams, C. C., Allison, J. G., Vidal, G. A., Burow, M. E., Beckman, B. S., Marrero, L., & Jones, F. E. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200403155 · Cited by 270
“Although the exact mechanism of STAT5A regulated nuclear retention of 4ICD remains unclear, retention of STAT proteins is mediated by an intrinsic DNA binding domain (Herrington et al., 1999; Meyer et al., 2003 ).”
BackgroundInteferons pen the JAK–STAT pathway
Schindler, C., & Plumlee, C. R. (2008) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2008.08.010 · Cited by 265
“[68] Meyer T, Marg A, Lemke P, Wiesner B, Vinkemeier U.”
BackgroundBrzózka, K. D., Finke, S., & Conzelmann, K. (2006) · Journal of Virology · doi:10.1128/jvi.80.6.2675-2683.2006 · Cited by 234
NLRP3 tyrosine phosphorylation is controlled by protein tyrosine phosphatase PTPN22
Spalinger, M. R., Kasper, S., Gottier, C., Lang, S., Atrott, K., Vavricka, S. R., Scharl, S., Gutte, P. M., Grütter, M. G., Beer, H., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci83669 · Cited by 236
Rabies Virus P Protein Interacts with STAT1 and Inhibits Interferon Signal Transduction Pathways
Vidy, A., Chelbi-alix, M., & Blondel, D. (2005) · Journal of Virology · doi:10.1128/jvi.79.22.14411-14420.2005 · Cited by 220
“Indeed, DNA-bound STAT1 is protected from dephosphorylation and is thus transiently retained in the nucleus (32, 33).”
BackgroundMultiple transcription factor families regulate axon growth and regeneration
Moore, D. L., & Goldberg, J. L. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20934 · Cited by 195
“Signaling is turned off when STATs are dephosphorylated in the nucleus by phosphatases (Haspel and Darnell, 1999), and exported back to the cytoplasm by nuclear export signals present within STATs’ DNA binding domains (McBride et al., 2000; Bhattacharya and Schindler, 2003; Meyer et al., 2003).”
BackgroundStats: Multifaceted Regulators of Transcription
Brierley, M. M., & Fish, E. N. (2005) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2005.25.733 · Cited by 197
“77 This DNA-bound Stat1 is protected from dephosphorylation, which is necessary for it to exit the nucleus.”
Marg, A., Shan, Y., Meyer, T., Meissner, T. B., Brandenburg, M., & Vinkemeier, U. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200403057 · Cited by 173
Self-citationTyrosine phosphorylation regulates the partitioning of STAT1 between different dimer conformations
Wenta, N., Strauss, H. M., Meyer, S., & Vinkemeier, U. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802130105 · Cited by 173
“It transforms the STATs into highaffinity DNA-binding transcriptional regulators and triggers their retention in the nucleus (3, 5, 6).”
Self-citationZhong, M., Henriksen, M. A., Takeuchi, K., Schaefer, O., Liu, B., ten Hoeve, J., Ren, Z., Mao, X., Chen, X., Shuai, K., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501063102 · Cited by 177
Camicia, R., Winkler, H. C., & Hassa, P. O. (2015) · Molecular Cancer · doi:10.1186/s12943-015-0474-2 · Cited by 177
“JAK1/2-mediated phosphorylation of STAT1 phosphorylation on Y701 enhances the nuclear shuttling by triggering the nuclear retention of the shuttling STAT1α and STAT1β, which are kept in the nucleus until tyrosine dephosphorylation occurs [498, 501, 502].”
BackgroundSadzak, I., Schiff, M., Gattermeier, I., Glinitzer, R., Sauer, I., Saalmüller, A., Yang, E., Schaljo, B., & Kovarik, P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801794105 · Cited by 166
Role of the JAK–STAT pathway in myocardial injury
Barry, S. P., Townsend, P. A., Latchman, D. S., & Stephanou, A. (2006) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.12.002 · Cited by 167
“75 Meyer, T. et al. (2003) DNA binding controls inactivation and nuclear accumulation of the transcription factorStat1.”
BackgroundSignal transducer and activator of transcription (STAT) signalling and T‐cell lymphomas
Mitchell, T. J., & John, S. (2005) · Immunology · doi:10.1111/j.1365-2567.2005.02091.x · Cited by 172
Vidy, A., Bougrini, J. E., Chelbi-alix, M., & Blondel, D. (2007) · Journal of Virology · doi:10.1128/jvi.01930-06 · Cited by 162
“Indeed, it has been proposed that DNA binding controls the nuclear accumulation of STAT1: DNA binding protects STAT1 from dephosphorylation, and the DNA-bound STAT1 is thus retained in the nucleus (17, 18, 19).”
BackgroundSTAT1 and pathogens, not a friendly relationship
Najjar, I., & Fagard, R. (2010) · Biochimie · doi:10.1016/j.biochi.2010.02.009 · Cited by 147
“its dephosphorylation on tyrosine 701, an event which occurs once STAT1 is released from its DNA target [69] (Fig.”
STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer
Awasthi, N. P., Liongue, C., & Ward, A. C. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01214-y · Cited by 155
“Alternatively, they may be uSTATs that result from dephosphorylation of nuclear pSTAT molecules [56].”
BackgroundNucleocytoplasmic shuttling of STAT transcription factors
Meyer, T., & Vinkemeier, U. (2004) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.2004.04423.x · Cited by 135
Self-citationSTAT signaling in mammary gland differentiation, cell survival and tumorigenesis
Haricharan, S., & Li, Y. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.03.014 · Cited by 135
Reich, N. C. (2013) · JAK-STAT · doi:10.4161/jkst.27080 · Cited by 131
Getting the message across, STAT! Design principles of a molecular signaling circuit
Vinkemeier, U. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200407163 · Cited by 116
“Although the intranuclear mobility of STAT dimers remains at the diffusion limit (Meyer et al., 2003, 2004), they are nonetheless trapped in this compartment until their tyrosine dephosphorylation.”
BackgroundResultInfluentialSelf-citationDynamics and non-canonical aspects of JAK/STAT signalling
Mohr, A., Chatain, N., Domoszlai, T., Rinis, N., Sommerauer, M., Vogt, M., & Müller‐Newen, G. (2011) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2011.09.005 · Cited by 113
Cooperativity of the MUC1 oncoprotein and STAT1 pathway in poor prognosis human breast cancer
Khodarev, N. N., Ahmad, R., Rajabi, H. N., Pitroda, S. P., Kufe, T., McClary, C., Joshi, M. D., MacDermed, D. M., Weichselbaum, R., & Kufe, D. W. (2009) · Oncogene · doi:10.1038/onc.2009.391 · Cited by 102
“This region contains a functional nuclear export signal that interacts with CRM1 and confers leptomycin B-sensitive export of nuclear STAT1 that has undergone tyrosine dephosphorylation (McBride et al., 2000; Meyer et al., 2003).”
BackgroundSTAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling
Begitt, A., Droescher, M., Meyer, T., Schmid, C., Baker, M., Antunes, F., Knobeloch, K., Owen, M., Naumann, R., Decker, T., et al. (2014) · Nature Immunology · doi:10.1038/ni.2794 · Cited by 102
Self-citationThe role of signal transducers and activators of transcription in colon cancer
Klampfer, L. (2007) · Frontiers in bioscience · doi:10.2741/2893 · Cited by 97
“In the nucleus, STAT1 is dephosphorylated and actively exported back to the cytoplasm by the chromosome region maintenance 1 (CRM1) export receptor (15-19).”
BackgroundApical role for BRG1 in cytokine-induced promoter assembly
Ni, Z., Karaskov, E., Yu, T., Callaghan, S. M., Der, S., Park, D. S., Xu, Z., Pattenden, S. G., & Bremner, R. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503070102 · Cited by 92
Meyer, T., Hendry, L., Begitt, A., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400766200 · Cited by 89
Self-citationHolloway, G., Truong, T. T., & Coulson, B. S. (2009) · Journal of Virology · doi:10.1128/jvi.01450-08 · Cited by 88
“At least for STAT1, DNA binding is required for its retention in the nucleus following translocation (35).”
BackgroundMolecular Basis for the Recognition of Phosphorylated STAT1 by Importin α5
Nardozzi, J. D., Wenta, N., Yasuhara, N., Vinkemeier, U., & Cingolani, G. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.07.013 · Cited by 85
“Notably, importin α5 (1-504) had slightly reduced binding affinity for pSTAT1 (Kd ~247 ± 27 nM) (Fig.”
Self-citationRatjadone and leptomycin B block CRM1‐dependent nuclear export by identical mechanisms
Meissner, T. B., Krause, E., & Vinkemeier, U. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.08.056 · Cited by 79
Self-citationA STAT3 dimer formed by inter-chain disulphide bridging during oxidative stress
Li, L., & Shaw, P. E. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.08.014 · Cited by 79
Lavaur, J., Bernard, F., Trifilieff, P., Pascoli, V., Kappès, V., Pagès, C., Vanhoutte, P., & Caboche, J. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2279-07.2007 · Cited by 83
“Thus, similarly to other transcription factors, including STAT 1 (Meyer et al., 2003), NF-AT4 (Shibasaki et al.”
BackgroundSekine, Y., Ikeda, O., Hayakawa, Y., Tsuji, S., Imoto, S., Aoki, N., Sugiyama, K., & Matsuda, T. (2007) · Oncogene · doi:10.1038/sj.onc.1210426 · Cited by 74
Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA
Liu, S., Jiang, M., Wang, W., Liu, W., Song, X., Ma, Z., Zhang, S., Liu, L., Liu, Y., & Cao, X. (2017) · Nature Immunology · doi:10.1038/s41590-017-0003-0 · Cited by 76
Nucleocytoplasmic shuttling revealed by FRAP and FLIP technologies
Köster, M., Frahm, T., & Häuser, H. (2004) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2004.11.002 · Cited by 74
Nakahira, M., Tanaka, T., Robson, B. E., Mizgerd, J. P., & Grusby, M. J. (2007) · Immunity · doi:10.1016/j.immuni.2007.01.010 · Cited by 76
“In contrast, TC-PTP appears to act as a nuclear PTP to inactivate STAT1 and STAT3 (Meyer et al., 2003; ten Hoeve et al., 2002), while PTP1B has been implicated as a cytoplasmic PTP, acting on STAT5 (Aoki and Matsuda, 2000).”
BackgroundInfluentialRosowski, E. E., Nguyen, Q., Camejo, A., Spooner, E., & Saeij, J. P. J. (2013) · Infection and Immunity · doi:10.1128/iai.01291-13 · Cited by 72
“Because STAT1 cannot be dephosphorylated until it has fallen off DNA (19), our previous observation that in cells preinfected with Toxoplasma IFN- -induced phospho-STAT1 levels were significantly higher than in uninfected cells (26) is consistent with this hypothesis.”
BackgroundResultInfluentialStructural and functional studies of STAT1 from Atlantic salmon (Salmo salar)
Skjesol, A., Hansen, T. E., Shi, C., et al. (2010) · BMC Immunology · doi:10.1186/1471-2172-11-17 · Cited by 68
“After activation of their target genes, STATs are dephosphorylated, released from the DNA and shuttled back to the cytoplasm [12,17,18].”
BackgroundActivated STAT1 Transcription Factors Conduct Distinct Saltatory Movements in the Cell Nucleus
Speil, J., Baumgart, E., Siebrasse, J. P., Veith, R., Vinkemeier, U., & Kubitscheck, U. (2011) · Biophysical Journal · doi:10.1016/j.bpj.2011.10.006 · Cited by 67
“A hallmark associated with STAT1 activation is the visible accumulation of activated dimers in the nucleus of cytokine-stimulated cells (7).”
BackgroundInfluentialSelf-citationHuang, Y., Qiu, J., Dong, S., Redell, M. S., Poli, V., Mancini, M. A., & Tweardy, D. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704548200 · Cited by 65
Chen, W., Daines, M., & Hershey, G. K. K. (2004) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2004.06.042 · Cited by 66
Knoblach, T., Grandel, B., Seiler, J., Nevels, M. M., & Paulus, C. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002016 · Cited by 62
“In fact, DNA binding was shown to protect STAT1 from dephosphorylation, which normally occurs at a step preceding export to the cytoplasm [132,133].”
BackgroundJägle, S., Heeg, M., Grün, S., Rensing‐Ehl, A., Maccari, M. E., Klemann, C., Jones, N., Lehmberg, K., Bettoni, C., Warnatz, K., et al. (2019) · Clinical Immunology · doi:10.1016/j.clim.2019.108316 · Cited by 63
Camicia, R., Bachmann, S. B., Winkler, H. C., Beer, M., Tinguely, M., Haralambieva, E., & Hassa, P. O. (2013) · Journal of Cell Science · doi:10.1242/jcs.118174 · Cited by 61
“JAK2 is thought to phosphorylate STAT1 on Y701 in the cytoplasm, whereas JAK1 seems to be required for phosphorylation on Y701 in the nucleus, preventing nuclear export of STAT1 (Meyer et al., 2003; Mowen and David, 2000).”
BackgroundNuclear Export Determines the Cytokine Sensitivity of STAT Transcription Factors
Loedige, I., Marg, A., Wiesner, B., Malecová, B., Oelgeschläger, T., & Vinkemeier, U. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509180200 · Cited by 62
Self-citationProtein Kinase Cδ Regulates Apoptosis via Activation of STAT1
DeVries, T. A., Kalkofen, R. L., Matassa, A. A., & Reyland, M. E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407448200 · Cited by 61
Mertens, C., Haripal, B., Klinge, S., & Darnell, J. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515876112 · Cited by 59
“It is known that the TC45 phosphatase is the responsible protein in the cell nucleus for dephosphorylation and that the purified enzyme will dephosphorylate DNA-free molecules in a cell-free context and the in vitro reaction can be inhibited by furnishing specific DNAbinding sites (37, 38).”
BackgroundMethodResultSignal transducers and activators of transcription—from cytokine signalling to cancer biology
Santos, C. I., & Costa‐Pereira, A. P. (2011) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2011.03.003 · Cited by 59
Droescher, M., Begitt, A., Marg, A., Zacharias, M., & Vinkemeier, U. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.235978 · Cited by 59
Self-citationGo in! Go out! Inducible control of nuclear localization
Ventura, B. D., & Kuhlman, B. A. (2016) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2016.06.009 · Cited by 54
Andrianifahanana, M., Singh, A. P., Némos, C., Ponnusamy, M. P., Moniaux, N., Mehta, P. P., Varshney, G. C., & Batra, S. K. (2007) · Oncogene · doi:10.1038/sj.onc.1210532 · Cited by 52
“dispensable for its nuclear localization in cells of different lineage (Chatterjee-Kishore et al., 2000; Meyer et al., 2003).”
BackgroundSong, L., Bhattacharya, S., Yunus, A. A., Lima, C. D., & Schindler, C. (2006) · Blood · doi:10.1182/blood-2006-04-020271 · Cited by 52
Liddle, F. J., Alvarez, J. V., Poli, V., & Frank, D. A. (2006) · Biochemistry · doi:10.1021/bi0525674 · Cited by 52
TRADD interacts with STAT1-α and influences interferon-γ signaling
Wesemann, D. R., Qin, H., Kokorina, N. A., & Benveniste, E. N. (2004) · Nature Immunology · doi:10.1038/ni1025 · Cited by 51
Buttmann, M., Berberich‐Siebelt, F., Serfling, E., & Rieckmann, P. (2006) · Journal of Vascular Research · doi:10.1159/000097977 · Cited by 50
“As expected, binding of STAT1 to the CCL2 GAS element was found to be reflected by the amount of tyrosine-phosphorylated nuclear STAT1, since phosphorylation of STAT1 at Y701 is necessary for the formation and DNA binding of STAT1 homo- or heterodimers at many GAS elements [”
BackgroundNovel role and mechanism of protein inhibitor of activated STAT1 in spatial learning
Tai, D. J. C., Hsu, W. L., Liu, Y. C., Ma, Y. L., & Lee, E. H. Y. (2011) · The EMBO Journal · doi:10.1038/emboj.2010.290 · Cited by 47
“…pull-down assay for STAT1 DNA-binding activity DNA oligonucleotides containing two GAS elements (underlined) (50-GAGACTCAGTTTCCCGTAAATCGTCCAGTTTCCCGTAAAGACTA TGC-30) were conjugated with a 50 biotin on the sense strand according to the method described previously (Meyer et al, 2003).”
MethodGuo, H., Kuang, S., Song, Q., Liu, M., Sun, X., & Yu, Q. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.99 · Cited by 45
Maiwald, T., Schneider, A., Busch, H. S., Sahle, S., Gretz, N., Weiß, T. S., Kummer, U., & Klingmüller, U. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07880.x · Cited by 45
Properties of STAT1 and IRF1 enhancers and the influence of SNPs
Hassan, M. A. E., Huang, K., Eswara, M. B. K., Xu, Z., Tao, Y., Aubry, A., Ni, Z., Livne-Bar, I., Sangwan, M., Ahmad, M. S., et al. (2017) · BMC Molecular Biology · doi:10.1186/s12867-017-0084-1 · Cited by 45
“The data here and other studies show that STAT1 and IRF1 can bind some sites in the basal state [21, 28], so in theory, low/unstable binding (undetectable by ChIP) could poise ISG enhancers.”
BackgroundResultHistone deacetylase inhibitors block IFNγ-induced STAT1 phosphorylation
Ginter, T., Bier, C., Knauer, S. K., Sughra, K., Hildebrand, D., Münz, T., Liebe, T., Heller, R., Henke, A., Stauber, R. H., et al. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.02.018 · Cited by 43
STAT1 Signaling Is Not Regulated by a Phosphorylation-Acetylation Switch
Antunes, F., Marg, A., & Vinkemeier, U. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05300-11 · Cited by 39
“used for immunoprecipitation (30) and Western blotting.”
BackgroundInfluentialSelf-citationMeyer, T., Begitt, A., & Vinkemeier, U. (2007) · FEBS Journal · doi:10.1111/j.1742-4658.2006.05626.x · Cited by 39
Self-citationLi, L., & Shaw, P. E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606940200 · Cited by 38
Complex systems biology approach to understanding coordination of JAK-STAT signaling
Soebiyanto, R. P., Sreenath, S. N., Qu, C., Loparo, K. A., & Bunting, K. D. (2007) · Biosystems · doi:10.1016/j.biosystems.2007.05.005 · Cited by 38
“Starting with the Wild-Type (WT) system - considered the nominal system, we conducted experiments with a pulsed input (various amplitude and durations), and observed the resulting concentration of one or more signaling components in which the phosphorylated nuclear STAT1 dimer is the main focus, as it is a proxy for p…”
BackgroundMethodC. elegans STAT: evolution of a regulatory switch
Wang, Y., & Levy, D. E. (2006) · The FASEB Journal · doi:10.1096/fj.06-6051com · Cited by 37
“Similarly, STAT1 nuclear accumulation has been tied to DNA binding (30, 31), but DNA binding independent mechanisms have recently been reported as well (32).”
BackgroundYong, L.-K., Lai, S., Liang, Z., Poteet, E. C., Chen, F., Buren, G. V., Fisher, W. P., Mo, Q., Chen, C., & Yao, Q. C. (2016) · Oncotarget · doi:10.18632/oncotarget.13704 · Cited by 38
“A few notable examples are: for Stat1, non-specific binding of DNA to the transcription factor protects it from dephosphorylation, retaining it in the nucleus [21]; for the GATA transcription factor GLN3, phosophorylation of the protein causes its binding to cytoplasmic protein URE2, preventing it from being transport…”
BackgroundZhang, Y., Takami, K., Lo, M. S., Huang, G., Yu, Q., Roswit, W. T., & Holtzman, M. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503263200 · Cited by 36
Rateitschak, K., Karger, A., Fitzner, B., Lange, F., Olaf Wolkenhauer, A., & Jaster, R. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.09.019 · Cited by 34
Functional Relevance of the Conserved DNA-binding Domain of STAT2
Brierley, M. M., & Fish, E. N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500426200 · Cited by 32
Holloway, G., Dang, V. T., Jans, D. A., & Coulson, B. S. (2014) · Journal of General Virology · doi:10.1099/vir.0.064063-0 · Cited by 32
“DNA binding plays an important role in the retention of STAT1 in the nucleus (Meyer et al., 2003), so interference with STAT1/2 DNA binding during rotavirus infection was possible.”
BackgroundInvolvement of STAT1 in proliferation and invasiveness of trophoblastic cells
de Sousa, F. L. P., Chaiwangyen, W., Prieto, D. M. M., et al. (2017) · Reproductive Biology · doi:10.1016/j.repbio.2017.05.005 · Cited by 31
Computational models of the JAK1/2-STAT1 signaling
Gambin, A., Charzyńska, A., Ellert‐Miklaszewska, A., & Rybiński, M. (2013) · JAK-STAT · doi:10.4161/jkst.24672 · Cited by 31
“22 Dimer dephosphorylation is a critical step, which enables the return of STAT1 to the cytosol to participate in additional rounds of the activation and deactivation cycle.”
BackgroundSystems biology of JAK/STAT signalling
Pfeifer, A. C., Timmer, J., & Klingmüller, U. (2008) · Essays in Biochemistry · doi:10.1042/bse0450109 · Cited by 33
STAT nuclear translocation: potential for pharmacological intervention
Meyer, T., & Vinkemeier, U. (2007) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.11.10.1355 · Cited by 31
“In a remarkable twist, the dephosphorylation reaction is proportional to the STAT DNA off-rate [53] .”
BackgroundSelf-citationInborn errors of immunity with loss- and gain-of-function germline mutations in STAT1
Asano, T., Utsumi, T., Kagawa, R., et al. (2022) · Clinical & Experimental Immunology · doi:10.1093/cei/uxac106 · Cited by 30
Brierley, M. M., Marchington, K. L., Jurišica, I., & Fish, E. N. (2006) · FEBS Journal · doi:10.1111/j.1742-4658.2006.05176.x · Cited by 30
IFN-type-I-mediated signaling is regulated by modulation of STAT2 nuclear export
Frahm, T., Häuser, H., & Köster, M. (2006) · Journal of Cell Science · doi:10.1242/jcs.02822 · Cited by 30
“IRF9 is a member of the interferon regulatory factor family characterized by a conserved N-terminal DNA-binding domain that binds to interferon-stimulated response elements (ISREs) (Nguyen et al., 1997).”
BackgroundPark, J., Son, M., Ho, C.-C., Lee, S.-H., Kim, Y., An, J., & Lee, S.-K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1054472 · Cited by 30
“To investigate the roles of STAT1 in the functional network of the T cell subset in vitro and in vivo under normal physiological conditions, we generated ndSTAT1-TMD, a fusion protein between Hph-1-PTD and STAT1-TMD derived as shown in Figure 1A. STAT1-TMD without Hph1-PTD was made as a negative control, and the mutat…”
BackgroundHüntelmann, B., Staab, J., Herrmann‐Lingen, C., & Meyer, T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097633 · Cited by 31
“Whole cell extracts from reconstituted U3A cells expressing wild-type or mutant STAT1 were incubated for 30 min with or without the recombinant Tc45 phosphatase in the absence or presence of 2xGAS, GAS-nonGAS or 2xnonGAS, as indicated.”
BackgroundMethodInfluentialSelf-citationInterleukins and STAT Signaling
Haque, S. J., & Sharma, P. (2006) · Vitamins and hormones · doi:10.1016/s0083-6729(06)74007-9 · Cited by 28
Yang, J., Kunimoto, H., Katayama, B., Zhao, H., Shiromizu, T., Wang, L., Ozawa, T., Tomonaga, T., Tsuruta, D., & Nakajima, K. (2019) · International Immunology · doi:10.1093/intimm/dxz061 · Cited by 25
Topolewski, P., Zakrzewska, K. E., Walczak, J., Nienałtowski, K., Müller‐Newen, G., Singh, A., & Komorowski, M. (2022) · Science Signaling · doi:10.1126/scisignal.abd9303 · Cited by 26
Novel roles of the CCR4–NOT complex
Chapat, C., & Corbo, L. (2014) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1254 · Cited by 24
Ruppert, V., Meyer, T., Pankuweit, S., Jónsdóttir, Þ., & Maisch, B. (2007) · Cardiovascular Pathology · doi:10.1016/j.carpath.2007.07.004 · Cited by 22
“This sequence of action, usually termed STAT activation, is accompanied by the rapid and transient nucleus accumulation of phosphorylated STAT1 [15,21].”
BackgroundSelf-citationAfroz, S., Brownlie, R. M., Fodje, M. N., et al. (2016) · Journal of Virology · doi:10.1128/jvi.00017-16 · Cited by 22
“The integrity of the DNA binding domain also determines nuclear retention of STAT1 (44).”
BackgroundCrisler, W. J., & Lenz, L. L. (2018) · Current Opinion in Immunology · doi:10.1016/j.coi.2018.05.014 · Cited by 23
Trilling, M., Le‐Trilling, V. T. K., & Hengel, H. (2012) · Future Microbiology · doi:10.2217/fmb.12.109 · Cited by 21
Nucleocytoplasmic Shuttling of STATs. A Target for Intervention?
Ernst, S., & Müller‐Newen, G. (2019) · Cancers · doi:10.3390/cancers11111815 · Cited by 20
“Amino acids in the DBD of STAT1 are involved in the recognition of Importin-α5 [65,66], connecting Importin-binding and nuclear presence with DNA-binding activity of STAT1 [91].”
BackgroundHuang, H., Zheng, Y., Li, L., Shi, W., Zhang, R., Liu, H., Chen, Z., & Wu, L. (2020) · Future Medicinal Chemistry · doi:10.4155/fmc-2020-0224 · Cited by 21
Asano, T., Noma, K., Mizoguchi, Y., Karakawa, S., & Okada, S. (2023) · Immunological Reviews · doi:10.1111/imr.13300 · Cited by 23
“7,14,15,16 Kagawa et al. 17 investigated the effect of STAT1 GOF variants on the conformational characteristics for dimerization through a comprehensive analysis based on alanine scanning.”
BackgroundSrinivasan, P., & Marić, M. (2010) · Immunology · doi:10.1111/j.1365-2567.2010.03355.x · Cited by 19
Petersen, J., Staab, J., Bader, O., Buhl, T., Ívetic, A., & Meyer, T. (2019) · Molecular Immunology · doi:10.1016/j.molimm.2019.07.008 · Cited by 17
Self-citationSong, L., & Schindler, C. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374145-5.00249-7 · Cited by 17
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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