A leading light in basic cancer research, Dr. Prives, Da Costa Professor of Biology in the Dept of Biological Sciences has transformed the field by immersing herself in characterizing the structure and function of the p53 tumor suppressor and its binding partners, notably Mdm2. She discovered that wild-type p53 is a sequence-specific DNA binding transcriptional activator, a finding that stimulated numerous studies devoted to identifying genes that regulate p53-mediated cellular outcomes. Her work has continues to the present to delve into the mechanisms but which wild-type p53 recognizes its cognate sites in DNA. She was also the first to demonstrate that SV40 large T antigen as well as the p53 missense mutations that are most common in cancer inhibit p53 transcription activation by interfering with p53 DNA-binding. Dr. Prives has further demonstrated that such mutant forms of p53 can inhibit the pro-apoptotic p53 homologues, p63 and p73. More recently she identified the mevalonic acid pathway as being promoted by cancer related mutant forms of p53 in breast cancer cells.
Dr. Prives showed that in response to genotoxic stress and DNA damage, wild-type p53 is phosphorylated at sites that weaken its interaction with Mdm2, its negative regulator. Work from her group also revealed that key sites on p53 are phosphorylated by checkpoint kinases 1 and 2 (Chk1/2). She has identified a number of regulators of Mdm2 including RPS7 (40S ribosomal protein S7) and TAB1 as being important in the p53 response to common chemotheraputics such as 5’FU (fluorouracil) and cisplatin.