Interaction of the Tumor Suppressor p53 with Replication Protein A.
Abstract
The DNA replication factor RPA physically associates with the tumor suppressor protein p53, an interaction that could be important for the function of both these proteins in normal and cancer cells. Using two mutant forms of p53 with the desired property of not binding RPA we have demonstrated that RPA binding is not required for growth suppression by p53. We have also made a deletion mutant of RPA which does not bind p53 to show that despite binding single-stranded DNA, this mutant of RPA fails to support DNA replication. Therefore the region of RPA which interacts with p53 is essential for the protein complex's activity. In contrast to RPA binding, transcription trans-activation by p53 is essential for growth suppression. One of targets of p53, p21/WAFl/CIPl, inhibits the cell-cycle by associating with cyclin-cdk kinases. It also inhibits DNA replication by interacting with a replication factor, Proliferating Cell Nuclear Antigen (PCNA). We have characterized a 39 amino acid fragment of p21 which can target PCNA in vitro and in vivo and suggest that small chemicals based on the structure of this peptide could be useful for targeting the DNA replication apparatus for chemotherapy of breast cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1996
- Accession Number
- ADA317025
Entities
People
- Anindya Dutta
Organizations
- Brigham and Women's Hospital