Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis.
Nat Cell Biol
; 17(10): 1356-69, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26389662
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cílios
/
Adenosina Trifosfatases
/
Proteínas de Ciclo Celular
/
Proteômica
/
Proteínas Adaptadoras de Transdução de Sinal
/
Mapas de Interação de Proteínas
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article