Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis.

ABSTRACT: The mutual interplay between epigenetic modifications and metabolic rewiring contributes to malignant features of prostate adenocarcinoma (PRAD). This study aimed to uncover the biological roles of deubiquitylase USP35 in PRAD and find effective epigenetic or metabolic targets. Bioinformatic tools or methods revealed that USP35 is upregulated in PRAD samples and correlates with inferior prognosis. The in vitro and in vivo assays suggested that USP35 could enhance malignant features of PRAD cells. Mechanistically, we found that USP35 could directly deubiquitinate and stabilize BRPF1 proteins. USP35 depends on accumulated BRPF1 proteins to accelerate cell growth, stem-like properties, and migration in vitro and in vivo. Interestingly, high BRPF1 could bind to promoter of SREBP2 and activate

SUBMITTER: Lin G 

PROVIDER: S-EPMC9649703 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature