Evidence map›Paper›PMID 12923054›Full record

ArticleGenes & development2003

DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1.

Thomas Meyer, Andreas Marg, Petra Lemke, Burkhard Wiesner, Uwe Vinkemeier

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 159 citations in OpenAlex.

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  15. Go in! Go out! Inducible control of nuclear localization.Current opinion in chemical biology · 2016
    Review
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  18. Review
  19. Mutations in the linker domain affect phospho-STAT3 function and suggest targets for interrupting STAT3 activity.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  20. Article

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Thomas MeyerAbteilung Zelluläre Signalverarbeitung, Freie Universität Berlin, Forschungsinstitut für Molekulare Pharmakologie, 13125 Berlin, Germany.
Andreas Marg
Petra Lemke
Burkhard Wiesner
Uwe Vinkemeier
Institut für Informationsverarbeitung · DELeibniz-Forschungsinstitut für Molekulare Pharmakologie · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Active Transport, Cell NucleusAntibodies, MonoclonalCell NucleusCytoplasmDNADNA-Binding ProteinsEnzyme InhibitorsHeLa CellsHumansInterferon-gammaModels, BiologicalMutationPhosphorylationRecombinant ProteinsSTAT1 Transcription FactorTrans-ActivatorsAntibodies, MonoclonalDNADNA-Binding ProteinsEnzyme InhibitorsInterferon-gammaRecombinant ProteinsSTAT1 protein, humanSTAT1 Transcription FactorTrans-ActivatorsTyrosineVanadates

Identifiers

PMID12923054
PMCPMC196254
OpenAlexW2099132542

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.