EZH2-induced lysine K362 methylation enhances TMPRSS2-ERG oncogenic activity in prostate cancer.
Adenocarcinoma
/ genetics
Animals
Enhancer of Zeste Homolog 2 Protein
/ genetics
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Lysine
/ metabolism
Male
Mice
Mice, Knockout
Oncogene Proteins
/ genetics
Oncogene Proteins, Fusion
/ genetics
Prostatic Neoplasms
/ genetics
Protein Conformation
Protein Processing, Post-Translational
Sequence Alignment
Serine Endopeptidases
/ genetics
Trans-Activators
/ metabolism
Transcription Factors
/ genetics
Transcriptional Regulator ERG
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 07 2021
06 07 2021
Historique:
received:
27
10
2020
accepted:
08
06
2021
entrez:
7
7
2021
pubmed:
8
7
2021
medline:
27
7
2021
Statut:
epublish
Résumé
The TMPRSS2-ERG gene fusion is the most frequent alteration observed in human prostate cancer. However, its role in disease progression is still unclear. In this study, we uncover an important mechanism promoting ERG oncogenic activity. We show that ERG is methylated by Enhancer of zest homolog 2 (EZH2) at a specific lysine residue (K362) located within the internal auto-inhibitory domain. Mechanistically, K362 methylation modifies intra-domain interactions, favors DNA binding and enhances ERG transcriptional activity. In a genetically engineered mouse model of ERG fusion-positive prostate cancer (Pb-Cre4 Pten
Identifiants
pubmed: 34230470
doi: 10.1038/s41467-021-24380-6
pii: 10.1038/s41467-021-24380-6
pmc: PMC8260656
doi:
Substances chimiques
ERG protein, mouse
0
Oncogene Proteins
0
Oncogene Proteins, Fusion
0
TMPRSS2-ERG fusion protein, human
0
Trans-Activators
0
Transcription Factors
0
Transcriptional Regulator ERG
0
Enhancer of Zeste Homolog 2 Protein
EC 2.1.1.43
Ezh2 protein, mouse
EC 2.1.1.43
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, mouse
EC 3.4.21.-
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4147Références
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