© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 7, 594-598,
April 7, 1999
© 1999 Oxford University Press
REVIEW |
The Emerging p53 Gene Family
Affiliations of author: Howard Hughes Medical Institute and Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
Correspondence to: William G. Kaelin, Jr., M.D., Dana-Farber Cancer Institute, Mayer Bldg., Rm. 457, 44 Binney St., Boston, MA 02115 (e-mail: william_kaelin{at}dfci.harvard.edu).
Perturbation of p53 protein function is a common, if not universal, finding in human cancer. Tumor suppression by p53 is due, at least in part, to its ability to activate transcription of certain genes involved in cell cycle control and apoptosis (programmed cell death). Two additional members of the mammalian p53 family, p73 and p51, which is also known as p40, p63, KET, or p73L, were recently identified. Both of these proteins share substantial sequence homology with p53 and can, at least when overproduced, activate p53-responsive promoters and induce apoptosis. Nonetheless, data on differences between these proteins and p53 are emerging. For example, p73 is not induced by DNA damage and is not targeted for inactivation by viral oncoproteins such as simian virus 40 (SV40) T antigen, adenovirus E1B 55K, and human papillomavirus E6. In contrast to p53, neither p73 nor p51 appears to be frequently mutated in human cancers on the basis of the limited studies reported to date. Finally, unlike p53, cells produce multiple p73 and p51 isoforms as a result of alternative splicing, and production of p73 and p51 appears to be restricted to certain tissues. Additional studies are required to determine the role, if any, that p73 and p51 play in cell growth control and carcinogenesis.
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