Ubiquitin-specific protease 13 promotes colorectal cancer progression by stabilizing mitogen-activated protein kinase kinase 3.

ABSTRACT: The deubiquitinase ubiquitin-specific protease 13 (USP13) has been implicated in various cancers, yet its precise molecular function and clinical significance in colorectal cancer (CRC) remain poorly defined. Here, we identify USP13 as a critical regulator of CRC progression through systematic investigation of its impact on oncogenic signaling pathways. Using luciferase-based pathway screening, we discovered that USP13 activates the mitogen-activated protein kinase (MAPK) signaling cascade. USP13 directly interacts with and stabilizes mitogen-activated protein kinase kinase 3 (MKK3), a key upstream kinase of the p38/MAPK pathway, through removal of K48-linked ubiquitination at the K32 residue. This deubiquitination process requires the UBA domain of USP13 and prevents proteasomal degradati

SUBMITTER: Chang SY 

PROVIDER: S-EPMC12660564 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature