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Nat Cell Biol. 2015 Oct;17(10):1356-69. doi: 10.1038/ncb3238. Epub 2015 Sep 21.

Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis.

Author information

1
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
2
Department of Systems Biology, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
3
Renal Division, Brigham and Women's Hospital, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
4
Department of Medicine, New Research Building, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
5
Department of Health Science and Technology, New Research Building, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
6
Harvard-MIT, Division of Health Sciences and Technology, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.

Abstract

The AAA-ATPase VCP (also known as p97 or CDC48) uses ATP hydrolysis to 'segregate' ubiquitylated proteins from their binding partners. VCP acts through UBX-domain-containing adaptors that provide target specificity, but the targets and functions of UBXD proteins remain poorly understood. Through systematic proteomic analysis of UBXD proteins in human cells, we reveal a network of over 195 interacting proteins, implicating VCP in diverse cellular pathways. We have explored one such complex between an unstudied adaptor UBXN10 and the intraflagellar transport B (IFT-B) complex, which regulates anterograde transport into cilia. UBXN10 localizes to cilia in a VCP-dependent manner and both VCP and UBXN10 are required for ciliogenesis. Pharmacological inhibition of VCP destabilized the IFT-B complex and increased trafficking rates. Depletion of UBXN10 in zebrafish embryos causes defects in left-right asymmetry, which depends on functional cilia. This study provides a resource for exploring the landscape of UBXD proteins in biology and identifies an unexpected requirement for VCP-UBXN10 in ciliogenesis.

PMID:
26389662
PMCID:
PMC4610257
DOI:
10.1038/ncb3238
[Indexed for MEDLINE]
Free PMC Article

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