Structural Basis of CDK4 Inhibition by p18INK4
Abstract
The proteins involved in the G1 to S phase transition have been shown to be particularly important in carcinogenesis. Mainly, the disruptions of the pathways involving the pRb and the p53 tumor suppressors have been shown to be common in cancers. The inactivation of the pRb pathway is commonly achieved either by the mutational inactivation of pRb or INK4 tumor suppressors or by the uncontrolled over-expression of Cyclin D1. Cyclin D1 activates Cyclin Dependent Kinase 4/6 (CDK4/6) which phosphorylate pRb. The INK4 family of proteins are specific inhibitors of Cyclin D 1-CDK4/6 complexes. A recently identified protein, p19(ARF), which is an alternatively spliced transcript of p16(INK4a), has been shown to stabilize p53 by preventing its degradation in a DNA damage independent manner. This proposal is focused on the study of INK4 family of proteins, p19(ARF), and Cyclin D1. We present here the crystal structure of p18(INK4c) and its implications for CDK4/6 binding.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 1999
- Accession Number
- ADA380978
Entities
People
- Ravichandran Venkataramani
Organizations
- University of Pennsylvania