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 HIF1α deubiquitinating enzyme. By counteracting pVHL-mediated ubiquitination of HIF1α, USP8 maintains a basal expression of HIF1α and HIF transcriptional output in normoxia, including the repression of Rabaptin5, which is essential for endosome trafficking-mediated ciliogenesis.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Troilo A,Alexander I,Muehl S,Jaramillo D,Knobeloch KP,Krek Wdoi
10.1002/embr.201337688subject
Has Abstractpub_date
2014-01-01 00:00:00pages
77-85issue
1eissn
1469-221Xissn
1469-3178pii
embr.201337688journal_volume
15pub_type
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