A complex with poly(A)-binding protein and EWS facilitates the transcriptional function of oncogenic ETS transcription factors in prostate cells.
ERG
ETS factor
EWS
PABPC1
prostate cancer
transcription
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
11 Nov 2023
11 Nov 2023
Historique:
received:
14
03
2023
revised:
21
10
2023
accepted:
25
10
2023
pubmed:
14
11
2023
medline:
14
11
2023
entrez:
13
11
2023
Statut:
aheadofprint
Résumé
The ETS transcription factor ERG is aberrantly expressed in approximately 50% of prostate tumors due to chromosomal rearrangements such as TMPRSS2/ERG. The ability of ERG to drive oncogenesis in prostate epithelial cells requires interaction with distinct coactivators, such as the RNA-binding protein EWS. Here, we find that ERG has both direct and indirect interactions with EWS, and the indirect interaction is mediated by the poly-A RNA-binding protein PABPC1. PABPC1 directly bound both ERG and EWS. ERG expression in prostate cells promoted PABPC1 localization to the nucleus and recruited PABPC1 to ERG/EWS-binding sites in the genome. Knockdown of PABPC1 in prostate cells abrogated ERG-mediated phenotypes and decreased the ability of ERG to activate transcription. These findings define a complex including ERG and the RNA-binding proteins EWS and PABPC1 that represents a potential therapeutic target for ERG-positive prostate cancer and identify a novel nuclear role for PABPC1.
Identifiants
pubmed: 37956771
pii: S0021-9258(23)02481-X
doi: 10.1016/j.jbc.2023.105453
pmc: PMC10704431
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105453Subventions
Organisme : NCI NIH HHS
ID : R01 CA204121
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002529
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
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