The broad, lone term objective of the proposed research is to understand cell cycle regulation. This may lead to new strategies for the control of health problems associated with the cell cycle, such as cancer and growth defects. p57 can arrest the cell cycle by inhibiting the catalytic activity of cyclin-dependent kinases (Cdks). p57 thus acts as a potential negative growth regulator and candidate tumor suppressor. The proposed research will use modern biophysical and molecular biology techniques to elucidate the mechanism of cyclin A-Cdk2 inhibition by p57.
The specific aims are: 1. Determine the composition of the p57 inhibited cyclin A-Cdk2 complex using sedimentation equilibrium. 2. Characterize the structure of the p57 Cdk-inhibition domain by nuclear magnetic resonance. 3. Identify the amino acid residues of p57 that contribute to cyclin A-Cdk2 inhibition by site-directed mutagenesis of p 57. 4. Identify the amino acid residues of cyclin A and/or Cdk2 that interact with p57 by site-directed mutagenesis of cyclin A and Cdk2.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29GM055156-05
Application #
6342928
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Zatz, Marion M
Project Start
1997-01-01
Project End
2002-12-31
Budget Start
2001-01-01
Budget End
2002-12-31
Support Year
5
Fiscal Year
2001
Total Cost
$106,715
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523