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

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Adenosine Triphosphatases, Animals, Cell Cycle Proteins, Cilia, Cytoskeletal Proteins, HEK293 Cells, HeLa Cells, Humans, Immunoblotting, LLC-PK1 Cells, Microscopy, Confocal, Microscopy, Fluorescence, Morphogenesis, Protein Binding, Protein Interaction Mapping, Protein Interaction Maps, Proteomics, RNA Interference, Swine, Tumor Suppressor Proteins
Nat. Cell Biol.
Date: Oct. 01, 2015
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