Login to the DGSOM Faculty Profiles
Steven G. Clarke, Ph.D.

Laboratory Address:
Paul Boyer Hall 628, 637 & 638

Work Address:
Paul Boyer Hall 640

Affiliations
Research Interests
My laboratory studies the biochemistry of the aging process. We want to understand the role of spontaneous reactions that result in covalent alterations to proteins and the role of enzymatic reactions that can reverse at least some types of the damage. We have focused on the degradation of aspartic acid and asparagine residues and the subsequent metabolism of their racemized and isomerized derivatives. The alteration of these residues can represent a significant fraction of the irreversible damage to proteins and would be expected to contribute to the limitation of their useful lifetime and that of the organism as a whole. We are presently determining the biological role of protein methyltransferases that specifically modify proteins containing altered aspartyl residues. These enzymes can initiate the conversion of D-aspartyl residues to the L-configuration as well as the conversion of isopeptide linkages to normal peptide bonds. Such "repair" reactions may greatly increase the useful lifetime of cellular proteins. We are presently examining these reactions in humans, mice, nematodes, plants, and bacteria. In each case, we are taking advantage of the particular features of each system - the medical relevance in humans, the usefulness of transgenic mice gene knockouts, the ease of working with the relatively small genomes of Arabidopsis, Caenorhabditis elegans, and Escherichia coli. We have also been interested in understanding the role of protein carboxyl methyltransferases that may be involved in modulating the function of other regulatory proteins. In 1993 we discovered that protein phosphatase 2A, the major dephosphorylating enzyme involved in both metabolism and cell cycle control, was itself methylated at its C-terminal leucine residue. Using the yeast Saccharomyces cerevisiae as an experimental system, we are taking both biochemical and genetic approaches to rationalize this methylation reaction. Finally, again using yeast as a model system, we are searching for novel methyltransferases that may regulate as yet unknown pathways.
Biography

Steven Clarke has been on the faculty of the UCLA Department of Chemistry and Biochemistry since 1978. He is currently a Distinguished Professor of Biochemistry and Director of the UCLA Cellular and Molecular Biology Training Program. He was born in Los Angeles and attended public schools in Altadena and Pasadena, California. He did his undergraduate work at Pomona College in Claremont, majoring in Chemistry and Zoology. During this time, he did undergraduate research at the UCLA Brain Research Institute with Dr. James E. Skinner and Professor Donald Lindsley on neural mechanisms of attention. He was also an NIH fellow in the laboratory of Dr. Peter Mitchell at Glynn Research Laboratories in Bodmin, England studying mitochondrial amino acid transport. He obtained his PhD in Biochemistry and Molecular Biology at Harvard University working as an NSF Fellow with Professor Guido Guidotti on membrane protein-detergent interactions and the identification of the major rat liver mitochondrial polypeptides as enzymes of the urea cycle. He returned to California to do postdoctoral work as a Miller Fellow at the University of California, Berkeley, with Professor Dan Koshland, identifying membrane receptors for bacterial chemotaxis. His research at UCLA has focused on roles of novel protein methyltransferases in aging and biological regulation highlighted by discoveries of the protein L-isoaspartyl repair methyltransferase, the isoprenylcysteine protein methyltransferase, and the protein phosphatase 2A methyltransferase. He has been a visiting scholar at Princeton University (1986-87), the University of Washington (2004-2005), and Vanderbilt University (2015).

Publications
Error in include template "/web/fdb5/www/gpb/institution/publications": can't read "allow_redirect_p": no such variable