Structural Basis of CDK4 Inhibition by p18INK4
Abstract
The proteins involved in the G1 to S phase transition have been shown to he particularly important in carcinogenesis. Mainly, the disruptions of the pathways involving the pRb and the p53 tumor suppressors have been shown to he common in cancers. Inactivation of the pRb pathway is commonly achieved either by the mutational inactivation of pPb or INK4 tumor suppressors or by the uncontrolled over-expression of Cyclin D1. Cyclin D1 activates CDK4/G which phosphorylate pPb. The INK4 proteins are specific inhibitors of Cyclin D1-CDK4/6 complexes. We have previously determined the structure of p18(sup INK4c). We have prepared more stable single amino-acid mutants of p18(sup INK4c). We are currently conducting urea denaturation experiments to estimate quantitatively the increase in stability. We are also using these mutants in cell cycle assays to determine if the increase in stability correlates with increase in activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2000
- Accession Number
- ADA392235
Entities
People
- Ravichandran Venkataramani
- Ronen Marmorstein
Organizations
- University of Pennsylvania