AACR-Women in Cancer Research Charlotte Friend Memorial Lectureship

SPOTLIGHT

14th Lectureship Recipient   Carol L. Prives, Ph.D. DaCosta Professor Columbia University New York, NY

Dr. Carol L. Prives delivered her lecture entitled, Lessons Learned from Studying the p53 Tumor Suppressor, during the 102nd AACR Annual Meeting 2011. The award was presented by Dr. Martine F. Roussel, Selection Committee Chairperson and Dr. Ann D. Thor, WICR Chairperson.

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Dr. Carol L. Prives is honored for her groundbreaking and world-renowned contributions in the understanding of the regulation and function of the p53 tumor suppressor protein.

Dr. Prives came into the p53 field from her studies of SV40 gene expression.  p53 had been previously discovered by others as a protein that binds to SV40 T antigen.  Prives was the first to purify biochemically tractable amounts of the p53 protein which enabled her and Bert Vogelstein to make the critical discovery that p53 is a sequence-specific DNA binding protein that functions as a transcription factor.  This work also showed that the common tumor-derived mutant forms of p53 are defective in DNA binding and transcriptional activation.  Further, the Prives group showed that SV40 T antigen disables the DNA binding activity of p53 which likely contributes to the ability of T antigen to transform cells.  These findings laid the groundwork for all of our understanding of how p53 works, for example the way in which the response to p53 is determined.  It is hard to overestimate how important this body of work is - both in our understanding of p53 as a tumor suppressor, and to explain the role of mutant p53 proteins found frequently in cancers.

Dr. Prives has also made exceptional contributions to our understanding of how p53 is regulated.  She has made numerous important discoveries, including the first indication of how stress such as DNA damage might signal to stabilize p53 - by promoting the phosphorylation of p53, which inhibits its interaction with the ubiquitin ligase (MDM2) that normally targets p53 for degradation.  Her work has also provided some important insights into the way MDM2 itself is regulated and how the choice of response to p53 might be controlled by other factors.  Very recently, she and her colleagues reported that glutaminase (GLS2) is a transcriptional target of p53, contributing to our rapidly growing understanding of the role of p53 in metabolism.  She has also provided critical insights into the regulation and function of the p53-related proteins, most importantly showing that p63 and p73 can form a complex and be regulated by mutant p53.

Taken together, Dr. Prives has made, and continues to make an exceptional contribution to our understanding of the regulation and function of p53.  She has been pivotal to many aspects of this important area of research, not only playing a key role in untangling the biology of p53 but also in pointing the way to the utilization of these studies for the development of novel cancer therapies.  Dr. Prives is a world-renowned scientist - her publication record is outstanding - and she is a talented and exceptional teacher.  She has mentored numerous young scientists through her laboratory, and they are now taking their place as the next generation of leaders in the field.  In addition to her formidable credentials as a scientist, Dr. Prives has also paved the way as a clear leader among women in science.  She serves as an example of how a stellar scientific career can be combined with family and personal life without compromising either endeavor.