| First Author | den Besten W | Year | 2012 |
| Journal | Nat Struct Mol Biol | Volume | 19 |
| Issue | 5 | Pages | 511-6, S1 |
| PubMed ID | 22466964 | Mgi Jnum | J:245285 |
| Mgi Id | MGI:5915908 | Doi | 10.1038/nsmb.2269 |
| Citation | den Besten W, et al. (2012) NEDD8 links cullin-RING ubiquitin ligase function to the p97 pathway. Nat Struct Mol Biol 19(5):511-6, S1 |
| abstractText | 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. |
