This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This research is focused on understanding how the cell cycle is regulated by ubiquitin-mediated proteolysis using x-ray crystallography as a primary tool. Progression through the cell cycle is coordinated by the cyclin-dependent kinases (CDKs) and their activating cyclin subunits as well as a series of CKI inhibitors. Control of the oscillations of the cyclins and CKIs by ubiquitin-dependent proteolysis plays a critical role in cell cycle regulation. Deregulation of the cyclins and CKIs can cause aberrant proliferation and genomic instability. Indeed, the eukaryotic cell cycle is one of the most frequently altered cellular processes identified in cancer. The overall goal of this research is to use SCF ubiquitin ligases as a model system to elucidate the structural and mechanistic basis of substrate recognition, lysine specificity, ubiquitin transfer, and the role of CDK in CKI degradation. My long-term objective is to gain a detailed understanding of the structure, function, and regulation of APC/C and Cul3-based ubiquitin ligases, and to use this knowledge to elucidate how defects of the ubiquitin system can lead to cancer and neurodegenerative diseases.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR012408-15
Application #
8363353
Study Section
Special Emphasis Panel (ZRG1-BCMB-R (40))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
15
Fiscal Year
2011
Total Cost
$3,843
Indirect Cost
Name
Brookhaven National Laboratory
Department
Type
DUNS #
027579460
City
Upton
State
NY
Country
United States
Zip Code
11973
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