Abstract: Series 115, Lecture 4

The Harvey Lectures Series 115 (2019—2020)

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Lecture #4: Thursday, February 13, 2020 — Watch Video of Lecture

Unexpected findings concerning the p53-Mdm2-MdmX axis in human cancer cells

Carol Prives, PhD

Carol Prives, PhD

Da Costa Professor of Biological Sciences

Columbia University

New York, New York

Dr Prives's Website

The Tp53 gene, which has the distinction of being mutated with very high frequency in many human cancers, encodes the most well scrutinized protein in cancer biology. Yet, despite decades of research, the functions and the activities of p53 and its negative regulators Mdm2 and MdmX are still not well understood. We study p53 from biochemical and biological perspectives and have uncovered novel p53-regulated pathways that reveal its multifaceted roles in different cellular contexts. On the other hand, while most well examined as negative regulators of p53, Mdm2 and MdmX are now understood to have p53-independent roles in cells, most of which are consistent with promoting oncogenesis. Our recent discoveries, however, provide support for these two proteins working in some cellular settings to facilitate tumor suppression both in p53-dependent and p53-independent settings. Our findings reveal the complexity of studying the p53-Mdm2-MdmX network and may provide the framework for future research and therapeutic interventions.