Evidence map›Paper›PMID 10022878›Full record

ArticleMolecular and cellular biology1999

The significance of tetramerization in promoter recruitment by Stat5.

S John, U Vinkemeier, E Soldaini, J E Darnell, W J Leonard

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
6.6field-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

74 citing papers in PubMed, 211 citations in OpenAlex.

  1. Article
  2. Article
  3. Strategies to therapeutically modulate cytokine action.Nature reviews. Drug discovery · 2023
    Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Tetramerization of STAT5 promotes autoimmune-mediated neuroinflammation.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  9. Dynamic Roles for IL-2-STAT5 Signaling in Effector and Regulatory CD4Journal of immunology (Baltimore, Md. : 1950) · 2020
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. STAT5B: A Differential Regulator of the Life and Death of CD4Journal of immunology (Baltimore, Md. : 1950) · 2018
    Article
  16. STAT5-mediated chromatin interactions in superenhancers activate IL-2 highly inducible genes: Functional dissection of theProceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  17. Article
  18. Article
  19. Review
  20. Article

14 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 3 institutions in 1 country.

S JohnLaboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674, USA.
U Vinkemeier
E Soldaini
J E Darnell
W J Leonard
National Heart Lung and Blood Institute · USNational Institutes of Health · USRockefeller University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Stat5a and Stat5b are rapidly activated by a wide range of cytokines and growth factors, including interleukin-2 (IL-2). We have previously shown that these signal transducers and activators of transcription (STAT proteins) are key regulatory proteins that bind to two tandem gamma interferon-activated site (GAS) motifs within an IL-2 response element (positive regulatory region III [PRRIII]) in the human IL-2Ralpha promoter. In this study, we demonstrate cooperative binding of Stat5 to PRRIII and explore the molecular basis underlying this cooperativity. We demonstrate that formation of a tetrameric Stat5 complex is essential for the IL-2-inducible activation of PRRIII. Stable tetramer formation of Stat5 is mediated through protein-protein interactions involving a tryptophan residue conserved in all STATs and a lysine residue in the Stat5 N-terminal domain (N domain). The functional importance of tetramer formation is shown by the decreased levels of transcriptional activation associated with mutations in these residues. Moreover, the requirement for STAT protein-protein interactions for gene activation from a promoter with tandemly linked GAS motifs can be relieved by strengthening the avidity of protein-DNA interactions for the individual binding sites. Taken together, these studies demonstrate that a dimeric but tetramerization-deficient Stat5 protein can activate only a subset of target sites. For functional activity on a wider range of potential recognition sites, N-domain-mediated oligomerization is essential.

Indexed as

Milk ProteinsPromoter Regions, GeneticBase SequenceBinding SitesCell Line, TransformedDimerizationDNADNA-Binding ProteinsHumansMolecular Sequence DataMutagenesisReceptors, Interleukin-2Response ElementsSTAT5 Transcription FactorTrans-ActivatorsTranscriptional ActivationDNADNA-Binding ProteinsMilk ProteinsReceptors, Interleukin-2STAT5A protein, humanSTAT5B protein, humanSTAT5 Transcription FactorTrans-ActivatorsTumor Suppressor Proteins

Identifiers

PMID10022878
PMCPMC83984
OpenAlexW2119802871

What OpenQuestion holds

Texttitle and abstract
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.