Besten WD, et al. (2012) NEDD8 links cullin-RING ubiquitin ligase function to the p97 pathway.LID - 10.1038/nsmb.2269 [doi] Nat Struct Mol Biol ()
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.
|Status: Epub ahead of print||Type: Journal Article||PubMed ID: 22466964|
Topics addressed in this paper
- To go to the Locus page for a gene, click on the gene name.
|Non-Fungal Related Genes/Proteins|