Viral Oncoproteins Discriminate between p53 and the p53 Homolog p73

ABSTRACT

p73 is a recently identified member of the p53 family. Previously it was shown that p73 can, when overproduced in p53-defective tumor cells, activate p53-responsive promoters and induce apoptosis. In this report we describe the generation of anti-p73 monoclonal antibodies and confirm that two previously described p73 isoforms are produced in mammalian cells. Furthermore, we show that these two isoforms can bind to canonical p53 DNA-binding sites in electrophoretic mobility shift assays. Despite the high degree of similarity between p53 and p73, we found that adenovirus E1B 55K, simian virus 40 T, and human papillomavirus E6 do not physically interact with p73. The observation that viral oncoproteins discriminate between p53 and p73 suggests that the functions of these two proteins may differ under physiological conditions. Furthermore, they suggest that inactivation of p73 may not be required for transformation.

ACKNOWLEDGMENTS

M.C.M. and C.A.J. contributed equally to this work.

We thank Arnold Berk, Herta Chao, Erik Flemington, Ed Harlow, Peter Howley, John Huibregste, Shuntaro Ikawa, and Joseph Nevins for reagents, Sorab Dalal for help with the GST-E6 binding assays, Ratna K. Vadlamudi for help with the p53 degradation assays, and members of the Kaelin laboratory for useful discussions.

M.C.M. was supported by an NIH training grant to the Cancer Biology Program at the Dana-Farber Cancer Institute. W.G.K. received support from the NIH and Novartis Pharmaceuticals and is a Howard Hughes Medical Institute assistant investigator.