Effect of ubiquitin protease system on DNA damage response in prostate cancer (Review).

ABSTRACT: Genomic instability is an essential hallmark of cancer, and cellular DNA damage response (DDR) defects drive tumorigenesis by disrupting genomic stability. Several studies have identified abnormalities in DDR-associated genes, and a dysfunctional ubiquitin-proteasome system (UPS) is the most common molecular event in metastatic castration-resistant prostate cancer (PCa). For example, mutations in Speckle-type BTB/POZ protein-Ser119 result in DDR downstream target activation deficiency. Skp2 excessive upregulation inhibits homologous recombination repair and promotes cell growth and migration. Abnormally high expression of a deubiquitination enzyme, ubiquitin-specific protease 12, stabilizes E3 ligase MDM2, which further leads to p53 degradation, causing DDR interruption and genomic instabi

SUBMITTER: Lin Y 

PROVIDER: S-EPMC10731405 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature