Evidence map›Paper›PMID 26396186›Full record

ArticleThe Journal of biological chemistry2015

Regulation of E2 promoter binding factor 1 (E2F1) transcriptional activity through a deubiquitinating enzyme, UCH37.

Christina S Mahanic, Varija Budhavarapu, Joshua D Graves, Gang Li, Weei-Chin Lin

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. De novo variants in RYBP are associated with a severe neurodevelopmental disorder and congenital anomalies.Genetics in medicine : official journal of the American College of Medical Genetics · 2025
    Article
  3. Review
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  9. Review
  10. E2F1 sumoylation as a protective cellular mechanism in oxidative stress response.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. TGF-β signaling pathway mediated by deubiquitinating enzymes.Cellular and molecular life sciences : CMLS · 2019
    Review
  16. Article
  17. Article
  18. Regulation of E2F1 Transcription Factor by Ubiquitin Conjugation.International journal of molecular sciences · 2017
    Review
  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

5 authors at 1 institution in 1 country.

Christina S MahanicFrom the Section of Hematology/Oncology and Integrative Molecular and Biomedical Sciences Graduate Program, Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030.
Varija BudhavarapuFrom the Section of Hematology/Oncology and.
Joshua D GravesFrom the Section of Hematology/Oncology and Integrative Molecular and Biomedical Sciences Graduate Program, Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030.
Gang LiFrom the Section of Hematology/Oncology and.
Weei-Chin LinFrom the Section of Hematology/Oncology and Integrative Molecular and Biomedical Sciences Graduate Program, Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030 weeichil@bcm.edu.
Baylor College of Medicine · US

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9M
Virology CoreP30AI036211 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI BUTEL, JANET S · 1994 to 2015
$21.7M
TRAINING PROGRAM IN CELL AND MOLECULAR BIOLOGYT32GM008231 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI NELSON, DAVID LOREN · 1990 to 2019
$7.2M
The ATM/E2F1 Pathway in DNA Damage and Growth ControlR01CA100857 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LIN, WEEI-CHIN · 2004 to 2019
$4.8M
Therapeutic Targeting of Oncogenic Stress in Cancer TreatmentR01CA138641 · NCI · BAYLOR COLLEGE OF MEDICINE · PI LIN, WEEI-CHIN · 2010 to 2014
$1.5M
BD Biosciences Special Order LSRIIS10RR024574 · NCRR · BAYLOR COLLEGE OF MEDICINE · PI LUMPKIN, ELLEN A · 2009 to 2009
$430k
NCI NIH HHS P30 CA125123NCI NIH HHS R01 CA100857NCI NIH HHS R01CA100857NCI NIH HHS R01 CA138641NCI NIH HHS R01CA138641NCRR NIH HHS S10 RR024574NIAID NIH HHS P30 AI036211NIGMS NIH HHS T32 GM008231NIGMS NIH HHS T32GM008231
6 · The paper itself

Abstract

E2F1 is tightly controlled by multiple mechanisms, but whether ubiquitination regulates its transcriptional activity remains unknown. Here we identify UCH37 as the first, to our knowledge, deubiquitinating enzyme for E2F1. UCH37 does not deubiquitinate UbK48 chains or affect E2F1 protein stability. Instead, UCH37, but not a catalytically dead mutant, decreases the Lys-63-linked ubiquitination of E2F1 and activates its transcriptional activity. UCH37 depletion reduces the gene expression of both proliferative and pro-apoptotic E2F1 target genes. UCH37 depletion also decreases both cell proliferation and apoptosis induction in functional assays. Interestingly, UCH37 expression is induced by E2F1, and its level rises in G1/S transition and S phase, suggesting a positive feedback loop between UCH37 and E2F1. UCH37 protein and mRNA levels are also induced after DNA damage. UCH37 localizes to the promoters of E2F1 pro-apoptotic target genes such as caspase 3, caspase 7, PARP1, and Apaf-1 and activates their expression after DNA damage. Moreover, the expression of E2F1 proliferative and pro-apoptotic genes is correlated with the levels of UCH37 in many primary tumors. These results uncover a novel mechanism for E2F1 transcriptional activation through removal of its Lys-63-linked ubiquitination by UCH37.

Indexed as

E2F1 Transcription FactorGene Expression Regulation, EnzymologicHEK293 CellsHumansPromoter Regions, GeneticRNA, MessengerS PhaseTranscription, GeneticUbiquitinationUbiquitin ThiolesteraseE2F1 protein, humanE2F1 Transcription FactorRNA, MessengerUbiquitin ThiolesteraseUCHL5 protein, humanapoptosisdeubiquitylation (deubiquitination)DNA damageE2F1transcription regulationubiquitylation (ubiquitination)UCH37/UCHL5

Identifiers

PMID26396186
PMCPMC4646310
OpenAlexW2243342146

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.