| First Author | Dai RM | Year | 2001 |
| Journal | Nat Cell Biol | Volume | 3 |
| Issue | 8 | Pages | 740-4 |
| PubMed ID | 11483959 | Mgi Jnum | J:159080 |
| Mgi Id | MGI:4441139 | Doi | 10.1038/35087056 |
| Citation | Dai RM, et al. (2001) Valosin-containing protein is a multi-ubiquitin chain-targeting factor required in ubiquitin-proteasome degradation. Nat Cell Biol 3(8):740-4 |
| abstractText | The ubiquitin-proteasome (Ub-Pr) degradation pathway regulates many cellular activities, but how ubiquitinated substrates are targeted to the proteasome is not understood. We have shown previously that valosin-containing protein (VCP) physically and functionally targets the ubiquitinated nuclear factor kappaB inhibitor, IkappaBalpha to the proteasome for degradation. VCP is an abundant and a highly conserved member of the AAA (ATPases associated with a variety of cellular activities) family. Besides acting as a chaperone in membrane fusions, VCP has been shown to have a role in a number of seemingly unrelated cellular activities. Here we report that loss of VCP function results in an inhibition of Ub-Pr-mediated degradation and an accumulation of ubiquitinated proteins. VCP associates with ubiquitinated proteins through the direct binding of its amino-terminal domain to the multi-ubiquitin chains of substrates. Furthermore, its N-terminal domain is required in Ub-Pr-mediated degradation. We conclude that VCP is a multi-ubiquitin chain-targeting factor that is required in the degradation of many Ub-Pr pathway substrates, and provide a common mechanism that underlies many of the functions of VCP. |
