tailieunhanh - Báo cáo khoa học: Evolutionary divergence of valosin-containing protein ⁄cell division cycle protein 48 binding interactions among endoplasmic reticulum-associated degradation proteins

Insulin-like growth factors (IGFs) play essential roles in fetal and postnatal growth and development of mammals. They are secreted by a wide variety of tissues, with the liver being the major source of circulating IGFs, and regulate cell growth, differentiation and survival. | Evolutionary divergence of valosin-containing proteinzcell division cycle protein 48 binding interactions among endoplasmic reticulum-associated degradation proteins Giacomo Morreale Laura Conforti John Coadwell Anna L. Wilbrey and Michael P. Coleman Laboratory of Molecular Signalling The Babraham Institute Cambridge UK Keywords endoplasmic reticulum-associated degradation Hrd1 Ube4b ubiquitin ligase valosin-containing protein Correspondence G. Morreale The Babraham Institute B501 Babraham Research Campus Babraham Cambridge CB22 3AT UK Fax 44 1223 496348 Tel 44 1223 496251 E-mail Centro di Ricerca per la Viticoltura Via Casoni 13 A 31058 Susegana TV Italy Fax 39-0438-738058 Tel 39-0438-73264 E-mail Received 21 August 2008 revised 9 December 2008 accepted 16 December 2008 doi Endoplasmic reticulum ER -associated degradation ERAD is a cell-autonomous process that eliminates large quantities of misfolded newly synthesized protein and is thus essential for the survival of any basic eukaryotic cell. Accordingly the proteins involved and their interaction partners are well conserved from yeast to mammals and Saccharomyces cerevisiae is widely used as a model system with which to investigate this fundamental cellular process. For example valosin-containing protein VCP and its yeast homologue cell division cycle protein 48 Cdc48p which help to direct polyubiquitinated proteins for proteasome-mediated degradation interact with an equivalent group of ubiquitin ligases in mouse and in S. cerevisiae. A conserved structural motif for cofactor binding would therefore be expected. We report a VCP-binding motif VBM shared by mammalian ubiquitin ligase E4b Ube4b -ubiquitin fusion degradation protein 2a Ufd2a hydroxymethylglutaryl reductase degradation protein 1 Hrdl -synoviolin and ataxin 3 and a related sequence in Mr 78 000 glycoprotein-Amfr with slightly different binding properties and .