Scholar Profile

Mark W. Hochstrasser

Professor
Department of Molecular Biophysics and Biochemistry
Yale University
266 Whitney Ave.
Bass Rm. 223
P.O. Box 208114
New Haven, CT 06520-8114
Voice: 203-432-6507(lab)
Email: mark.hochstrasser@yale.edu
Personal Homepage
1992 Searle Scholar

Research Interests

Protein Turnover in Eukaryotes

Selective protein degradation frequently underlies the ability of cells to switch between differentiated states. As a model for analyzing protein degradation as a regulatory mechanism, we are studying how the yeast Saccharomyces cerevisiae develops into alternate cell types. Interconversion between the two haploid cell types of this organism can be extremely efficient, and our work indicates that selective protein turnover is critical for this process. We have found that the alpha2 repressor, a transcriptional regulator involved in cell type control, is rapidly degraded in vivo. Ubiquitin is an evolutionarily conserved polypeptide found free or covalently joined to a variety of cellular proteins and is involved in functions as diverse as DNA repair, cell cycle control, and the stress response. In many cases, conjugation to ubiquitin marks the target protein for degradation by a large and abundant intracellular protease called the 26S proteasome. We have found that alpha2 is degraded by several ubiquitin-dependent mechanisms in vivo. Using a combination of genetic, biochemical, and molecular approaches, we are seeking to identify and characterize both the molecular determinants that target specific proteins for proteolysis and the enzymatic machinery responsible for their recognition and destruction.