Parp7 generates an ADP-ribosyl degron that controls negative feedback of androgen signaling.

ABSTRACT: The androgen receptor (AR) transduces the effects of circulating and tumor-derived androgens to the nucleus through ligand-induced changes in protein conformation, localization, and chromatin engagement. Defining how these events are integrated with signal transduction is critical to understand how AR drives prostate cancer and unveil pathway features that are potentially amenable to therapeutic intervention. We describe a novel post-transcriptional mechanism that controls AR levels on chromatin and gene output based on highly selective, inducible degradation. We find that the mono-ADP-ribosyltransferase PARP7 generates an ADP-ribosyl degron in the DNA-binding domain of AR, which is recognized by the ADP-ribose reader domain in the ubiquitin E3 ligase DTX2 and degraded by the proteasome. M

SUBMITTER: Wierbilowicz K 

PROVIDER: S-EPMC12402299 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature