Role of the Cdk Inhibitor Sic 1 in Start
Abstract
Cancer is essentially a disease of inappropriate proliferation due to a loss of normal cell cycle controls. The scope of this work was to study how cell cycle regulation by G1-phase Cyclin dependent kinases (Cdks) relates to breast cancer causation. The purpose of this proposal was to use yeast as an experimental system to examine the role of G1-Cdks in promoting cell cycle progression. The three major findings of this proposal are detailed below. First, we have shown that G1 cyclins are constitutively unstable and rate limiting for cell cycle progression 1. Second, the only essential function of G1 cyclins is to phosphorylate the B-type Cdk inhibitor, Sic1, and target it for degradation 2. Third, Sicl is one of few known in vivo substrates of yeast G1-Cdks 3. Sic1 mutants lacking several phosphorylation sites are stabilized and completely block cell cycle progression 1,3. Thus, the amount and phosphorylation state of Sic1 appears to determine the timing and size of cell division 3. By studying the mechanism of cell cycle control, we can begin to understand how cell cycle defects leads to abnormal proliferation, and how by preventing inappropriate proliferation, we may be able to reduce the incidence of breast cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA388144
Entities
People
- Brandt Schneider
Organizations
- Texas Tech University Health Sciences Center