Cellular Proteins Interacting with the Tumor Suppressor Protein p53.
Annual rept. 15 Jul 95-14 Jul 96,
BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
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Tumor suppressor protein p53 interacts directly with the DNA replication factor RPA and inhibits its ability to bind single-strand-DNA. We defined the domain of p53 that bound to RPA and constructed p53 mutants that failed to bind RPA, but still functioned as transcriptional activators. We found that while these mutants of p53 lost their ability to bind RPA they still maintained the growth suppression function of p53. Growth suppression function of p53 is dependent on its transactivation activity, probably by inducing p21 and other cell cycle inhibitors. We have extended our study to the p2l protein, which is induced by p53 and interacts with both the cdk2 Icinase and a DNA replication factor PcNA. Here we have demonstrated the importance of PCNA-inhibitory domain of p21 in vivo. We have also shown that p21 has to interact directly with both cyclin subunit and cdk2 subunit of the cyclin-cdk complex in order to inhibit the kinase activity and suppress cell growth in vivo.
- Medicine and Medical Research