This application requests partial funding for a conference on Ubiquitin and Intracellular Protein Degradation to be held 28 June 1997 through 3 July 1997 at the conference Center of Vermont Academy, Saxtons River, VT. This Biennial conference, which was initiated in 1989, is sponsored by and receives partial funding from the Federation of the American Societies of Experimental Biology (FASEB). It is the only regularly scheduled international meeting devoted to this important area of research. The mechanisms and regulation of intracellular protein degradation are of fundamental importance in determining the overall protein content and steady state levels of particular intracellular proteins. The central pathway of protein turnover within eucaryotes is ubiquitin- and ATP-dependent and requires the 26S proteasome. Ubiquitin is a low molecular weight, highly conserved polypeptide that exerts it biological effect through its covalent conjugation to other proteins in an enzymatic pathway requiring ATP hydrolysis. The ligation of ubiquitin to proteins, or more correctly the formation of multiubiquitin chains, serves as a recognition signal for binding of the target protein to the 26S proteasome through specific interaction with subunit 5a of the 19S regulatory complex of the proteasome. This pathway is responsible for the degradation of constitutively and conditionally short-lived proteins including those of abnormal structure generated by environmental stress or mutation as well as various other key regulatory proteins including transcription factors, oncogenes, membrane receptors, and cyclins. The 1997 meeting will be organized into nine sessions comprised of five talks each. Two sessions, comprised of seven talks each, will be composed of speakers chosen from submitted abstracts of participants based on scientific content with special attention given to younger investigators. Ample time will be reserved between all presentations for questions and discussion by the audience. In addition, two poster sessions are planned to allow all participants to present recent findings.
