Acetylation-dependent regulation of BRAF oncogenic function.

ABSTRACT: Aberrant BRAF activation, including the BRAF^V600E mutation, is frequently observed in human cancers. However, it remains largely elusive whether other types of post-translational modification(s) in addition to phosphorylation and ubiquitination-dependent regulation also modulate BRAF kinase activity. Here, we report that the acetyltransferase p300 activates the BRAF kinase by promoting BRAF K601 acetylation, a process that is antagonized by the deacetylase SIRT1. Notably, K601 acetylation facilitates BRAF dimerization with RAF proteins and KSR1. Furthermore, K601 acetylation promotes melanoma cell proliferation and contributes to BRAF^V600E inhibitor resistance in BRAF^V600E harboring melanoma cells. As such, melanoma patient-derived K601E oncogenic mutation

SUBMITTER: Dai X 

PROVIDER: S-EPMC8813213 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature