Rapid changes in cell physiology during cell cycle transitions or in response to changes in external conditions are often mediated by the degradation of regulatory molecules. These changes are typically directed by the modification of protein targets with chains of the small protein ubiquitin. Ubiquitinization is carried out by a series of three enzymes, sometimes referred to as E1, E2 and E3, which function in tandem to transfer ubiquitin to a substrate. Substrate specificity is usually mediated by the E3 complex, also called a ubiquitin ligase. The SCF and the APC represent two highly conserved multi-subunit ubiquitin ligases important for both cell cycle progression and the regulation of many aspects of cellular physiology. We will examine mechanisms of APC regulation, and also identify the substrates of these and other ubiquitin ligases using a comprehensive screening technique that we have recently developed.

Public Health Relevance

Cancer is the result of uncontrolled cell division. In this proposal, we outline experiments that characterize proteins responsible for the regulation of cell division. In doing this, we can better understand how cancers arise and the characteristics of tumors that can be used to selectively target them.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM070539-06
Application #
7627944
Study Section
Cellular Signaling and Regulatory Systems Study Section (CSRS)
Program Officer
Zatz, Marion M
Project Start
2004-06-01
Project End
2012-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
6
Fiscal Year
2009
Total Cost
$324,450
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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