USP9X destabilizes pVHL and promotes cell proliferation.

ABSTRACT: Numerous mutations of the Von Hippel-Lindau (VHL) gene have been reported to cause dysfunction of VHL protein (pVHL) and lead to processes related to tumor progression. pVHL acts as an E3 ligase and degrades downstream targets, such as hypoxia-inducible transcription factor (HIF) which is essential for tumor growth. Previous studies reported reduction of VHL protein, rather than mRNA in VHL-related tumor patients, suggesting that instability of the pVHL protein itself is a primary cause of dysfunction. Regulation of pVHL stability has therefore been a major focus of research. We report that ubiquitin-specific protease 9X (USP9X), which is a deubiquitinase binds and promotes degradation of both wild-type and mutants of pVHL that retain E3 ligase function, thus activating the HIF pathway. US

SUBMITTER: Zhang C 

PROVIDER: S-EPMC5312400 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature