Evidence map›Paper›PMID 22378781›Full record

ArticleThe Journal of biological chemistry2012

Mechanisms of unphosphorylated STAT3 transcription factor binding to DNA.

Olga A Timofeeva, Sergey Chasovskikh, Irina Lonskaya, Nadya I Tarasova, Lyuba Khavrutskii, Sergey G Tarasov, Xueping Zhang, Valeriy R Korostyshevskiy, Amrita Cheema, Lihua Zhang and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
6.7field-weighted citation impact, top 2% of its field
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

81 citing papers in PubMed, 134 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Cellular signaling meets bacterial infection: the integrative role of STAT3.Frontiers in cellular and infection microbiology · 2026
    Review
  6. STAT3 SH2 Domain Aspartic Acid 661 Mutations Activate Immune Gene Programs.Journal of cellular and molecular medicine · 2026
    Article
  7. STAT3 axis in cancer and cancer stem cells: From oncogenesis to targeted therapies.Biochimica et biophysica acta. Reviews on cancer · 2025
    Review
  8. Article
  9. NovelImmune network · 2025
    Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. STAT3 Role in T-Cell Memory Formation.International journal of molecular sciences · 2022
    Review

21 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

13 authors at 2 institutions in 1 country.

Olga A TimofeevaDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC 20057, USA.
Sergey Chasovskikh
Irina Lonskaya
Nadya I Tarasova
Lyuba Khavrutskii
Sergey G Tarasov
Xueping Zhang
Valeriy R Korostyshevskiy
Amrita Cheema
Lihua Zhang
Sivanesan Dakshanamurthy
Milton L Brown
Anatoly Dritschilo
Georgetown University · USFrederick National Laboratory for Cancer Research · US

Funding

X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI DANIEL P SILVER · 1995 to 2026
$94.8M
CCR Biophysics Resource CoreZICBC010965 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TARASOV, SERGEY · 2009 to 2025
$10.5M
Inhibitors of protein-protein interactionsZIABC011306 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TARASOVA, NADYA · 2010 to 2025
$7.3M
Intramural NIH HHSNCI NIH HHS CA56036-08NCI NIH HHS P30 CA056036
6 · The paper itself

Abstract

Phosphorylation of signal transducer and activator of transcription 3 (STAT3) on a single tyrosine residue in response to growth factors, cytokines, interferons, and oncogenes activates its dimerization, translocation to the nucleus, binding to the interferon γ (gamma)-activated sequence (GAS) DNA-binding site and activation of transcription of target genes. STAT3 is constitutively phosphorylated in various cancers and drives gene expression from GAS-containing promoters to promote tumorigenesis. Recently, roles for unphosphorylated STAT3 (U-STAT3) have been described in response to cytokine stimulation, in cancers, and in maintenance of heterochromatin stability. However, the mechanisms underlying U-STAT3 binding to DNA has not been fully investigated. Here, we explore STAT3-DNA interactions by atomic force microscopy (AFM) imaging. We observed that U-STAT3 molecules bind to the GAS DNA-binding site as dimers and monomers. In addition, we observed that U-STAT3 binds to AT-rich DNA sequence sites and recognizes specific DNA structures, such as 4-way junctions and DNA nodes, within negatively supercoiled plasmid DNA. These structures are important for chromatin organization and our data suggest a role for U-STAT3 as a chromatin/genome organizer. Unexpectedly, we found that a C-terminal truncated 67.5-kDa STAT3 isoform recognizes single-stranded spacers within cruciform structures that also have a role in chromatin organization and gene expression. This isoform appears to be abundant in the nuclei of cancer cells and, therefore, may have a role in regulation of gene expression. Taken together, our data highlight novel mechanisms by which U-STAT3 binds to DNA and supports U-STAT3 function as a transcriptional activator and a chromatin/genomic organizer.

Indexed as

Binding SitesCell Line, TumorChromatinDNAFemaleGene Expression Regulation, NeoplasticHumansKineticsMaleMicroscopy, Atomic ForcePhosphorylationPlasmidsProtein BindingProtein IsoformsProtein Structure, TertiarySTAT3 Transcription FactorChromatinDNAProtein IsoformsSTAT3 Transcription Factor

Identifiers

PMID22378781
PMCPMC3340179
OpenAlexW2023546541

What OpenQuestion holds

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LicenceCC BY-NC
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.