Evidence map›Paper›PMID 24682819›Full record

ArticleNucleic acids research2014

Functional redundancy between the transcriptional activation domains of E2A is mediated by binding to the KIX domain of CBP/p300.

Christopher M Denis, David N Langelaan, Alyssa C Kirlin, Seth Chitayat, Kim Munro, Holly L Spencer, David P LeBrun, Steven P Smith

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

19 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Review
  3. The Function of E2A in B-Cell Development.Advances in experimental medicine and biology · 2024
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Relationship between the structure and function of the transcriptional regulator E2A.Journal of biological research (Thessalonike, Greece) · 2021
    Review
  9. Mediator subunit MED1 is required for E2A-PBX1-mediated oncogenic transcription and leukemic cell growth.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Epistatic interactions between mutations of TACI (Clinical & translational immunology · 2017
    Article
  16. Article
  17. Article
  18. Article
  19. 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

8 authors at 1 institution in 1 country.

Christopher M DenisDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
David N LangelaanDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
Alyssa C KirlinDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
Seth ChitayatDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
Kim MunroProtein Function Discovery Group, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
Holly L SpencerDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
David P LeBrunProtein Function Discovery Group, Queen's University, Kingston, Ontario, K7L 3N6, Canada Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, K7L 3N6, Canada Division of Cancer Biology and Genetics, Cancer Research Institute, Queen's University, Kingston, Ontario, K7L 3N6, Canada steven.smith@queensu.ca.
Steven P SmithDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, K7L 3N6, Canada Protein Function Discovery Group, Queen's University, Kingston, Ontario, K7L 3N6, Canada steven.smith@queensu.ca.
Queen's University · CA

Funding

Canadian Institutes of Health Research MOP 106471Canadian Institutes of Health Research MOP 81333
6 · The paper itself

Abstract

The E-protein transcription factors play essential roles in lymphopoiesis, with E12 and E47 (hereafter called E2A) being particularly important in B cell specification and maturation. The E2A gene is also involved in a chromosomal translocation that results in the leukemogenic oncoprotein E2A-PBX1. The two activation domains of E2A, AD1 and AD2, display redundant, independent, and cooperative functions in a cell-dependent manner. AD1 of E2A functions by binding the transcriptional co-activator CBP/p300; this interaction is required in oncogenesis and occurs between the conserved ϕ-x-x-ϕ-ϕ motif in AD1 and the KIX domain of CBP/p300. However, co-activator recruitment by AD2 has not been characterized. Here, we demonstrate that the first of two conserved ϕ-x-x-ϕ-ϕ motifs within AD2 of E2A interacts at the same binding site on KIX as AD1. Mutagenesis uncovered a correspondence between the KIX-binding affinity of AD2 and transcriptional activation. Although AD2 is dispensable for oncogenesis, experimentally increasing the affinity of AD2 for KIX uncovered a latent potential to mediate immortalization of primary hematopoietic progenitors by E2A-PBX1. Our findings suggest that redundancy between the two E2A activation domains with respect to transcriptional activation and oncogenic function is mediated by binding to the same surface of the KIX domain of CBP/p300.

Indexed as

Transcriptional ActivationBinding SitesBone Marrow CellsModels, Molecularp300-CBP Transcription FactorsProtein Interaction Domains and MotifsProtein Structure, TertiaryTranscription Factor 3p300-CBP Transcription FactorsTranscription Factor 3

Identifiers

PMID24682819
PMCPMC4066744
OpenAlexW2143896637

What OpenQuestion holds

Textmetadata
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.