The majority of targeted protein degradation in the cell is performed by the ubiquitin (Ub)/26S proteasome pathway, which is highly conserved in all eukaryotic species. In this pathway, proteins to be degraded are covalently tagged with multiple ubiquitins, which serves as the degradation signal, by the sequential action of three enzymes. The final enzyme in this process, the E3 Ub-ligase, binds the target and catalyzes attachment of the Ub moiety to the protein. This proteolytic pathway has been shown to be important for a wide range of cellular processes, including cell cycle progression, DNA repair, hormone signal transduction and receptor regulation, and degradation of abnormal proteins. It also has been implicated genetically in a number of diseases, including cancer, Parkinson's disease, and muscular dystrophy, arguing for the need to study this pathway in more detail. One subfamily of E3 Ub-ligases is the SCF (Skpl, Cullin/Cdc53, F-box protein) complex. In Arabidopsis thaliana 19 genes encode Skpl homologues and 694 genes encode F-box proteins. Presumable the 19 ASKs combine with the 694 F-box proteins to generate a hierarchy of SCF complexes capable of labeling a wide range of targets. I propose a line of research that studies the functions of the ASK genes in Arabidopsis. By using genetic, biochemical, and cytological approaches to characterize the function of ASKs, I hope to better understand the roles that SCF complexes play in various cellular processes in Arabidopsis. The remarkable conservation of the Ub/26S proteasome pathway means these studies should contribute to our understanding of its function in all eukaryotes, which could lead to new strategies to affect the pathway for medicinal or agricultural benefit.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM068361-02
Application #
6747865
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Tompkins, Laurie
Project Start
2003-05-01
Project End
2006-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
2
Fiscal Year
2004
Total Cost
$47,296
Indirect Cost
Name
University of Wisconsin Madison
Department
Miscellaneous
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715