USP10 Regulates ZEB1 Ubiquitination and Protein Stability to Inhibit ZEB1-Mediated Colorectal Cancer Metastasis.

ABSTRACT: Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor that can promote tumor invasion and metastasis by inducing epithelial-to-mesenchymal transition (EMT). To date, regulation of ZEB1 by RAS/RAF signaling remains unclear, and few studies have examined posttranslation modification of ZEB1, including its ubiquitination. In human colorectal cancer cell lines with RAS/RAF/MEK/ERK activation, an interaction of ZEB1 with the deubiquitinase ubiquitin-specific protease 10 (USP10) was identified whereby USP10 modifies ZEB1 ubiquitination and promotes its proteasomal degradation. Regulation of the USP10-ZEB1 interaction by MEK-ERK signaling was shown whereby constitutive activation of ERK can phosphorylate USP10 at Ser236 to impair its interaction with ZEB1 and enable ZEB1 protein s

SUBMITTER: Sun L 

PROVIDER: S-EPMC10239320 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature