Signal induced phosphorylation of IkappaBalpha, the inhibitor of NF-kappaB leads to its subsequent poly-ubiquitination and degradation by the ubiquitin proteasome pathway. This allows NF-kappaB to translocate into the nucleus of the cell and turn on a variety of stress response genes. The specific ubiquitin ligase of IkappaBalpha has been reported to be SCFBTrCP, which is a multiprotein complex. BTrCP is an F-Box protein that also contains a WD40 repeat motif. The F-box region of the protein binds Skp1, Cul1, and mediates the binding of an E2 (Ubch5c). The WD40 repeat motif binds phophorylated IkBa. A homolog of BTrCP is BTrCP2. The purpose of this grant is to determine whether BTrCP2 is a relevant IkB E3-ligase. And to understand the mechanism of E2 specificity associated with SCF ubiquitin ligase complexes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31GM068979-03
Application #
6945730
Study Section
Special Emphasis Panel (ZRG1-F05 (29))
Program Officer
Gaillard, Shawn R
Project Start
2003-09-01
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
3
Fiscal Year
2005
Total Cost
$28,815
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Pineda, Gabriel; Ea, Chee-Kwee; Chen, Zhijian J (2007) Ubiquitination and TRAF signaling. Adv Exp Med Biol 597:80-92