Rare Diseases >> Abstract Details   The UBE2G2 Binding Domain in the Ubiquitin Ligase GP78 and Methods of Use Thereof Description of Invention: Cytosolic and nuclear proteins are targeted for proteosomal degradation by the addition of multiubiquitin chains. The specificity of this process is largely conferred by ubiquitin protein ligases (E3s) that interact with specific ubiquitin conjugating enzymes (E2s). One important role for ubiquitylation is in quality control in the secretory pathway, targeting proteins for degradation through a set of processes known as endoplasmic reticulum (ER) -associated degradation (ERAD). ERAD is important in many diseases including cystic fibrosis, neurodegenerative disorders, alpha-1 antitrypsin deficiency, tyrosinase deficiency and cancer. ERAD is also important in controlling levels of cell surface receptors and in regulation crucial enzymes involved in cholesterol metabolism. gp78, also known as the autocrine motility factor receptor, is an E3 implicated in ERAD. This invention relates to the identification of a discrete domain within gp78 that encodes a binding site specific for gp78’s cognate E2, Ube2g2. Ube2g2 is the most widely implicated E2 in ERAD. Expression of the Ube2g2 binding region provides a means of blocking ERAD by preventing interactions between gp78 and Ube2g2 and has the potential to provide diagnostic and therapeutic methods of intervening in modulating ERAD with consequences for disease processes and for generating recombinant secreted proteins in mammalian cells. Inventors: Allan Weissman et al. (NCI) Patent Status: DHHS Reference No. E-244-2004/0 -- U.S. Provisional Application No. 60/583,263 filed 26 Jun 2004 PCT Application No. PCT/US2005/14635 filed 27 Apr 2005, which published as WO 2006/007023 on 19 Jan 2006 U.S. Patent Application No. 11/597,453 filed 21 Nov 2006 Portfolios: Internal Medicine Internal Medicine-Diagnostics-Other Internal Medicine-Therapeutics-Other Internal Medicine-Diagnostics Internal Medicine-Therapeutics For Additional Information Please Contact: Surekha Vathyam Ph.D. Office of Technology Transfer 6011 Executive Blvd, Suite 325 Rockville, MD 20852-3804 Phone: 301/435-4076 Email: vathyams@mail.nih.gov Fax: 301/402-0220 Web Ref: 1016 Last Updated On: 1/05