Home Page for Carol Prives' Lab

Carol Prives

Columbia University
Biological Sciences
818A Fairchild Center, M.C. 2422
New York, N.Y. 10027
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Mutation of the p53 tumor suppressor gene is the most frequent lesion detected in cancer. Consequently, understanding the structure and function of the normal p53 protein and how it differs from the mutant p53 proteins that are commonly found in cancer patients' tumors should provide valuable information. When cells are induced to accumulate high levels of p53 by agents of stress such as DNA damage or hypoxia, they either undergo cell cycle arrest or programmed cell death. We and others have shown that p53 is a binding protein that can activate transcription from reporter templates bearing p53 binding sites. We have analyzed in detail the functional domains of p53 and how they are regulated by both covalent and non-covalent modifiers. A number of p53 t arget genes have been identified whose functions are relevant to cell arrest or apoptosis. However, in some cases p53 induces apoptosis in a transactivation-independent manner. Although p53 is widely studied there are several questions that remain about this important protein: How do cells transmit signals from genotoxic stress to activate p53? What are the downstream targets of p53 that are involved in its many functions in cells? What is the transactivation-independent function of p53 and how does it work? Finally, with respect to the central role that p53 plays in human cancer, can we use information derived from the basic research on this protein to develop p53-based cancer therapeutics? The search for answers to these and other questions are the basis for much of the work currently going on in our laboratory.

The cell cycle of higher eykaryotes requires the activity of a number of cyclin dependent protein kinases (CDKs). Although information has accumulated about how the CDKs themselves are regulated, less is known about the substrates of these enzymes whose phosphorylation leads to cell cycle regulation. An ongoing project in our laboratory is the study of a number of CDK substrates and how phosphorylation regulates their function. We are particularly interested in how CDKs affect DNA synthesis and DNA repair.

Representative Publications

Gottifredi, V., Shieh, S-Y, Taya ,Y., and C. Prives. (2001) P53 Accumulates but is Functionally Impaired when DNA Synthesis is Blocked. Proc. Natl. Acad. Sci. U.S.A. 98:1036-1041.

Gottifredi, V., Karni-Schmidt, O., Shieh, S-Y., and C. Prives. (2001). P53 down-regulates hCHK1 through p21. Mol. Cell. Biol 21:1066-1076..

Zhou, J., Ahn, J., Wilson, S., and C. Prives. (2001) A Role for p53 in Base Excision Repair. EMBO J.20 914-923.

Gaiddon C, Lokshin M., Ahn J. T. Zhang and Prives C. (2001). A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain. Mol Cell Biol. 21:1874-1887.

Shieh, S-Y., Ahn, J., Tamai, K., Taya, Y., and C. Prives. (2000). The human homologues of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage inducible sites. Genes &. Dev. 14: 289-300.

Ollmann, M., Young,L.M., Di Como, C.J. Karim, F., Belvin, M., Roberts, S., Whittaker, K., Demsky, M., Fisher, W.W., Buchman, A., Duyk,G., Friedman, L., Prives, C and C. Kopczynski (2000) Drosophila p53 is a Structural and Functional Homolog of the Tumor Suppressor p53. Cell 101: 91-101.

Cain, C., Miller, S., Ahn, J and C. Prives. (2000). The N-Terminus of p53 Regulates Its Dissociation From DNA. J. Biol. Chem. 275:39944-53.

Gaiddon, C., Moorthy, N.C. and C. Prives. (1999). Ref-1 regulates the transactivation and pro-apoptotic functions of p53 in vivo. EMBO J. 18: 5609-5621.

Di Como, C.J., Gaiddon, C. and C. Prives. (1999). p73 function is inhibited by tumor-derived p53 mutants in mammalian cells. Mol Cell Biol. 19: 1438-1499.

Shieh, S-Y., Taya, Y. and C. Prives. (1999). Oligomerization of p53 is required for DNA-damage-induced phosphorylation at the N-terminus of p53. EMBO J. 18:1815-1823.

Prives. C. (1998) Signalling to p53: breaking the p53:Mdm2 circuit. Cell.95: 5-8.

Shieh, S-Y., M. Ikeda, Y. Taya, and C. Prives. 1997. DNA damage- induced phosphorylation of p53 alleviates inhibition by mdm2. Cell 91: 325-334. Abstract

Jayaraman, L., Murthy, K.G.K., Curran, K., Xanthoudakis, S., and Prives, C. (1997) Identification of redox/repair protein Ref-1 as an activator of p53. Genes & Dev. 11:558-570.Abstract

Chen, X., Ko, L., Jayaraman, L. and Prives, C. (1996)p53 levels, functional domains and DNA damage determine the extent of the apoptotic response of tumor cells. Genes & Dev. 10:2438-2451.Abstract

Jayaraman, L. and C. Prives. (1995) Activation of p53 Sequence- specific DNA Binding by Short Single Strands of DNA Requires the p53 C-terminus. Cell 81: 1021-1029.

Wang, Y., and Prives, C. (1995) Increased and altered DNA bind ing of p53 by S and G2/M but not G1 cyclin dependent kinases. Nature, 376:88-91.

Prives, C. (1994) How loops, sheets and ` helices help us to understand p53. Cell 78:1-4.Abstract

Bargonetti, J., Manfredi, J., Chen, X., Marshak, D. and Prives, C. (1993) A proteolytic fragment of wild-type but not mutant p53 spanning the central conserved portion of the protein con- tains the sequence specific DNA binding domain. Genes & Dev. 7:2565-2574.Abstract

Farmer, G., Bargonetti, J., Zhu, H., Friedman, P., Prywes R., and Prives, C. (1992) Wild type p53 activates transcription in vitro. Nature 358:83-86.Abstract

Courses Taught:

Course Number



Biochemistry, II: Molecular Biology

Lab Members

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