NEDD8 links cullin-RING ubiquitin ligase function to the p97 pathway.
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.
Mesh Terms:
Adenosine Triphosphatases, Carrier Proteins, Cell Line, Cullin Proteins, DNA-Binding Proteins, Humans, Models, Molecular, Nuclear Proteins, Protein Interaction Domains and Motifs, Protein Interaction Maps, Ubiquitin, Ubiquitin-Protein Ligases, Ubiquitins
Adenosine Triphosphatases, Carrier Proteins, Cell Line, Cullin Proteins, DNA-Binding Proteins, Humans, Models, Molecular, Nuclear Proteins, Protein Interaction Domains and Motifs, Protein Interaction Maps, Ubiquitin, Ubiquitin-Protein Ligases, Ubiquitins
Nat. Struct. Mol. Biol.
Date: May. 01, 2012
PubMed ID: 22466964
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