Evidence map›Paper›PMID 20400516›Full record

ArticleThe Journal of biological chemistry2010

DNA binding by the ETS protein TEL (ETV6) is regulated by autoinhibition and self-association.

Sean M Green, H Jerome Coyne, Lawrence P McIntosh, Barbara J Graves

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

48 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Importin-9 recognizes the winged-helix fold of ETS transcription factors to mediate nuclear import.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Sticky, Adaptable, and Many-sided: SAM protein versatility in normal and pathological hematopoietic states.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. DNA binding induces aProceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. T315I-mutated myeloid sarcoma.Leukemia research reports · 2019
    Article
  19. Article
  20. Article
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

4 authors at 2 institutions in 2 countries.

Sean M GreenDepartment of Oncological Sciences, University of Utah School of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112-5550, USA.
H Jerome Coyne
Lawrence P McIntosh
Barbara J Graves
University of British Columbia · CAUniversity of Utah · US

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
Transcriptional Control Mechanisms by ETS FactorsR01GM038663 · NIGMS · UNIVERSITY OF UTAH · PI GRAVES, BARBARA J · 1992 to 2015
$3.9M
CIHRNCI NIH HHS P30 CA042014NCI NIH HHS P50CA42014NIGMS NIH HHS R01 GM038663NIGMS NIH HHS R01GM38663
6 · The paper itself

Abstract

The ETS protein TEL, a transcriptional repressor, contains a PNT domain that, as an isolated fragment in vitro, self-associates to form a head-to-tail polymer. How such polymerization might affect the DNA-binding properties of full-length TEL is unclear. Here we report that monomeric TEL binds to a consensus ETS site with unusually low affinity (K(d) = 2.8 x 10(-8) M). A deletion analysis demonstrated that the low affinity was caused by a C-terminal inhibitory domain (CID) that attenuates DNA binding by approximately 10-fold. An NMR spectroscopically derived structure of a TEL fragment, deposited in the Protein Data Bank, revealed that the CID consists of two alpha-helices, one of which appears to block the DNA binding surface of the TEL ETS domain. Based on this structure, we substituted two conserved glutamic acids (Glu-431 and Glu-434) with alanines and found that this activated DNA binding and enhanced trypsin sensitivity in the CID. We propose that TEL displays a conformational equilibrium between inhibited and activated states and that electrostatic interactions involving these negatively charged residues play a role in stabilizing the inhibited conformation. Using a TEL dimer as a model polymer, we show that self-association facilitates cooperative binding to DNA. Cooperativity was observed on DNA duplexes containing tandem consensus ETS sites at variable spacing and orientations, suggesting flexibility in the region of TEL linking its self-associating PNT domain and DNA-binding ETS domain. We speculate that TEL compensates for the low affinity, which is caused by autoinhibition, by binding to DNA as a cooperative polymer.

Indexed as

AlanineAmino Acid SequenceDNAETS Translocation Variant 6 ProteinGlutamic AcidHumansKineticsMolecular Sequence DataPolymersProtein BindingProtein ConformationProtein Structure, TertiaryProto-Oncogene Proteins c-etsRepressor ProteinsSequence Homology, Amino AcidStatic ElectricityAlanineDNAETS Translocation Variant 6 ProteinGlutamic AcidPolymersProto-Oncogene Proteins c-etsRepressor ProteinsTrypsin

Identifiers

PMID20400516
PMCPMC2881775
OpenAlexW1972021734

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.