Protein Arginine Methyltransferase 5 Promotes pICln-Dependent Androgen Receptor Transcription in Castration-Resistant Prostate Cancer.

ABSTRACT: The majority of advanced prostate cancer therapies aim to inhibit androgen receptor (AR) signaling. However, AR reactivation inevitably drives disease progression to castration-resistant prostate cancer (CRPC). Here we demonstrate that protein arginine methyltransferase 5 (PRMT5) functions as an epigenetic activator of AR transcription in CRPC, requiring cooperation with a methylosome subunit pICln. In vitro and in xenograft tumors in mice, targeting PRMT5 or pICln suppressed growth of CRPC cells. Full-length AR and AR-V7 transcription activation required both PRMT5 and pICln but not MEP50. This activation of transcription was accompanied by PRMT5-mediated symmetric dimethylation of H4R3 at the proximal AR promoter. Further, knockdown of PRMT5 abolished the binding of

SUBMITTER: Beketova E 

PROVIDER: S-EPMC7669631 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature