XPC Deficiency Activate Cisplatin-Mediated Autophagy in Bladder Cancer by Limiting Novel PHRF1-Mediated Ubiquitination of the p53 Protein.

ABSTRACT: Muscle-invasive bladder cancers (MIBC) are biologically heterogeneous and have widely variable conventional chemotherapy responses and clinical outcomes. This study demonstrates that XPC deficiency in bladder cancer cells can promote autophagy in response to the cisplatin-mediated DNA damage response (DDR). This process is closely related to both the overexpression of KDM4A and the downregulation of PHRF1 induced by the overactivation of ATM phosphate. The overaccumulation of KDM4A can suppress PHRF1 expression and result in significant nuclear accumulation of the p53 protein. Notably, this study defines a new mechanism by which PHRF1 regulates p53 posttranslationally through the ubiquitin-proteasome system. In XPC low expression cells, PHRF1 performs a more critical E3 ubiquitin ligase fu

SUBMITTER: Zhao B 

PROVIDER: S-EPMC12850319 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature