Action of the p53 Effector, p21, on its Targets: Cyclin-cdk and PCNA
Abstract
While studying the action of p21 on cyclin-cdks a 12 amino acid peptide, the Cy motif, was shown to be sufficient for inhibiting the protein kinase. The Cy motif was subsequently found on several substrates of cdks, where they are part of the substrate recognition sequence. A peptide containing the Cy motif inhibited the cdk competitively. In the last year we have developed an assay for small chemicals that mimic the action of a Cy peptide and used this assay to screen about 12,000 compounds in a synthetic chemical library. In addition, we have discovered that statins inhibit cancer cell proliferation by inhibiting the activating phosphorylation of cdk2. Analysis of the action of p21 on PCNA has also identified a small peptide that is used by p21 to interact with PCNA. Recent studies on the interaction of PCNA with Fen1 and DNA polymerase delta, have however indicated that such a p21 based peptide is unlikely to have differential inhibitory effects on the interaction of PCNA with Fen1 or polymerase delta and so will not be useful therapeutically.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADB282069
Entities
People
- Anindya Dutta
Organizations
- Brigham and Women's Hospital