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| the
life and death of proteins: regulation
by ubiquitin and the proteasome |
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Mark Hochstrasser, Ph.D.
Professor of Molecular
Biophysics & Biochemistry
Email: mark.hochstrasser@yale.edu
Web
site
B.A., Rutgers University,
1981;
Ph.D. UCSF 1987;
Postdoctoral Fellow, M.I.T., 1987-1990;
Assistant/Associate/Full Professor, University
of Chicago, 1990-2000;
Yale faculty 2000. |
The research in our laboratory can be grouped
into two broad and overlapping areas. First, we
wish to understand, at a mechanistic and molecular
level, how specific proteins are rapidly degraded
within eukaryotic cells even while most proteins
are spared. Such turnover is central to a great
variety of regulatory mechanisms, including many
of medical relevance. Much of this regulated degradation
occurs via the highly conserved ubiquitin-proteasome
system. The proteasome is a large, cylindrical
machine that fragments proteins into short peptides.
Second, we are analyzing the function and dynamics
of protein modification by other proteins. The
prototypical example of a protein that is covalently
attached to other proteins is ubiquitin, but in
recent years, evidence for at least a dozen such
systems has come to light. While ubiquitin generally
is used to mark its targets for destruction, the
consequences of protein ligation to the various
"ubiquitin-like proteins" are poorly
understood. One such protein that we study, called
SUMO, is attached to many proteins in vivo and
is crucial for cell-cycle progression. Much of
our work is conducted in the yeast Saccharomyces
cerevisiae, an organism that permits both facile
genetic manipulation and biochemical analysis.
Selected Publications
S.-J. Li and M. Hochstrasser (2003). The Ulp1
SUMO isopeptidase: Distinct domains required for
viability, nuclear envelope localization, and
substrate specificity. J. Cell Biology
160, 1069-1081.
D. Schwartz and M. Hochstrasser (2003). A superfamily
of protein tags: Ubiquitin, SUMO, and related
modifiers. Trends Biochem. Sciences 28, 321-328.
J.D. Laney and M. Hochstrasser (2003). Ubiquitin-dependent
degradation of the yeast Mata2 transcriptional
repressor enables a switch in developmental state.
Genes & Devel. 17, 2259-2270.
I. Velichutina, P.L. Connerly, C.S. Arendt, X.
Li, and M. Hochstrasser (2004) Plasticity in eukaryotic
20S proteasome ring assembly revealed by a subunit
deletion in yeast. EMBO J. 23, 500-510.
M. Hochstrasser (2004). Ubiquitin signalling:
What's in a chain? Nature Cell Biol. 6,
in press.
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