SPOP inhibits BRAF-dependent tumorigenesis through promoting non-degradative ubiquitination of BRAF.

ABSTRACT:

Background

The gene encoding the E3 ubiquitin ligase substrate-binding adapter Speckle-type BTB/POZ protein (SPOP) is frequently mutated in prostate cancer (PCa) and endometrial cancer (EC); however, the molecular mechanisms underlying the contribution of SPOP mutations to tumorigenesis remain poorly understood.

Methods

BRAF harbors a potential SPOP-binding consensus motif (SBC) motif. Co-immunoprecipitation assays demonstrated that BRAF interacts with SPOP. A series of functional analyses in cell lines were performed to investigate the biological significance of MAPK/ERK activation caused by SPOP mutations.

Results

Cytoplasmic SPOP binds to and induces non-degradative ubiquitination of BRAF, thereby reducing the interaction between BRAF and other core components of t

SUBMITTER: Feng K 

PROVIDER: S-EPMC9805134 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature