HIF1α 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 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 Rep

journal_title

EMBO reports

authors

Troilo A,Alexander I,Muehl S,Jaramillo D,Knobeloch KP,Krek W

doi

10.1002/embr.201337688

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

77-85

issue

1

eissn

1469-221X

issn

1469-3178

pii

embr.201337688

journal_volume

15

pub_type

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