HIF1α deubiquitination by USP8 is essential for ciliogenesis in normoxia.
- Troilo A Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
- Alexander I
- Muehl S
- Jaramillo D
- Knobeloch KP
- Krek W
- 2014-01-01
Published in:
- EMBO reports. - 2014
Animals
Cell Hypoxia
Cilia
Endocytosis
Endopeptidases
Endosomal Sorting Complexes Required for Transport
HEK293 Cells
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Mice
Oxygen
Protein Binding
Protein Stability
Protein Transport
Ubiquitin Thiolesterase
Ubiquitination
Vesicular Transport Proteins
Von Hippel-Lindau Tumor Suppressor Protein
English
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.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1002/embr.201337688
- PMID 24378640
- Persistent URL
- https://folia.unifr.ch/global/documents/88892
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