NEDD8 links cullin-RING ubiquitin ligase function to the p97 pathway.
Nat Struct Mol Biol
; 19(5): 511-6, S1, 2012 Apr 01.
Article
de En
| MEDLINE
| ID: mdl-22466964
ABSTRACT
The AAA+ ATPase p97 and its UBA-UBX cofactors are thought to extract ubiquitinated proteins from membranes or protein complexes as a prelude to their degradation. However, for many cofactors ubiquitinated targets have not yet been identified, leaving their biological function unclear. Previous analysis has linked the p97 pathway to cullin-RING ubiquitin ligases (CRLs); here we demonstrate that the human p97 cofactor UBXD7 mediates the p97-CRL interaction through its conserved ubiquitin-interacting motif (UIM). UBXD7 and its yeast ortholog, Ubx5, associate only with the active, NEDD8- or Rub1-modified form of cullins. Disruption of the Ubx5 UIM results in a loss of CRL binding and consequently impedes degradation of a Cul3 substrate. These results uncover an unexpected and conserved role for NEDD8 in linking CRL ubiquitin ligase function to the p97 pathway.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protéines nucléaires
/
Ubiquitines
/
Protéines de transport
/
Adenosine triphosphatases
/
Ubiquitin-protein ligases
Type d'étude:
Prognostic_studies
Limites:
Humans
Langue:
En
Journal:
Nat Struct Mol Biol
Sujet du journal:
BIOLOGIA MOLECULAR
Année:
2012
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique