Carol L. Prives
Columbia University
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Primary Section: 41, Medical Genetics, Hematology, and Oncology Secondary Section: 21, Biochemistry Membership Type:
Member
(elected 2008)
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Research Interests
My early interest in the SV40 DNA tumor virus as a model for eukaryotic gene expression and oncogenic transformation eventually led me to study the p53 tumor suppressor protein. P53 had been identified by others as a protein that stably associates with the viral large tumor (T) antigen. In our earlier studies we and others showed that p53 is a sequence specific regulator of transcription. We found that both the common tumor derived mutations within p53 protein as well as SV40 T antigen prevent p53 binding to and activation of its target genes. My group has since focused extensively on how p53 interacts with DNA, examining how covalent modifications and non-covalent modifiers regulate p53 DNA binding and transactivation of its target genes. We have become particularly intrigued with the many modes by which different p53 target genes are selectively regulated leading to different cellular outcomes such as cell cycle arrest and cell death. We have also examined the complex circuitry between p53 and its negative regulators Mdm2 and MdmX and our work has touched upon the roles of upstream regulators of p53 including the checkpoint kinases Chk1 and Chk2. Finally, I have had an ongoing interest in the complex interrelationships between p53 and its homologues p63 and p73.
