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UCSD researchers determine mechanism for degradation of G proteins

Researchers at the University of California, San Diego (UCSD) School of Medicine have identified a previously unknown component of the body's cellular garbage disposal called the ubiquitin system, which is responsible for regulation of cell function by removal of abnormal and unneeded proteins.

Published in the July 8, 2003 issue of Proceedings of the National Academy of Sciences, the study provides the first description of a molecule called GAIP interacting protein N terminus (GIPN) that plays a key role in the degradation of G proteins, which are switches that turn activities on or off in the cell.

Senior author Marilyn Farquhar, Ph.D., a UCSD professor and chair of the Department of Cellular and Molecular Medicine, noted the findings should be of interest to the pharmaceutical industry since G proteins regulate everything from hormone secretion to the beating of the heart.

The researchers found that GIPN appears to specifically target G proteins for degradation and thereby regulates G protein signaling by controlling the amount of G protein expressed in the cell. This occurs via GIPN binding to the N terminus of G alpha interacting proteins (GAIP), which is the mechanism that sets the ubiquitin system in motion.

The ubiquitin system is used extensively by the cell for the turnover and degradation of proteins in both the cytoplasm, the material surrounding the nucleus, and in cell membranes. Ubiquitin, itself, is a small peptide tag that marks a protein for destruction. The interaction of GIPN and GAIP, which was also discovered by the UCSD team, is part of the machinery that places the little ubiquitin tag on a protein.

A source of study by numerous research labs, the ubiquitin system is crucial for nearly every significant activity in the cell. Although this system of protein turnover was first identified in the 1930s, the molecular mechanisms responsible for the process have remained largely unknown.

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Contact: Sue Pondrom
spondrom@ucsd.edu
619-543-6163
University of California - San Diego
22-Jul-2003


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