HIF1? deubiquitination by USP8 is essential for ciliogenesis in normoxia.

ABSTRACT: Loss of primary cilia is a key feature of von Hippel-Lindau tumor suppressor (VHL)-associated pathology. Although VHL-deficiency predisposes cells to precipitous cilia disassembly in response to growth factor cues, it does not affect ciliogenesis. Here, using a siRNA-based screen to find genes that are essential for ciliogenesis only in the presence of the VHL tumor suppressor gene product pVHL, we identify ubiquitin-specific protease (USP)8. The pVHL-dependency of USP8 for ciliogenesis is directly linked to its function as a HIF1? deubiquitinating enzyme. By counteracting pVHL-mediated ubiquitination of HIF1?, USP8 maintains a basal expression of HIF1? and HIF transcriptional output in normoxia, including the repression of Rabaptin5, which is essential for endosome trafficking-mediated ciliogenesis.

SUBMITTER: Troilo A 

PROVIDER: S-EPMC4303451 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature