Adenovirus E4orf6 oncoprotein modulates the function of the p53-related protein, p73

  1. Fumihiro Higashino*,,
  2. James M. Pipas, and
  3. Thomas Shenk*,§
  1. *Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014; and Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260
  1. Contributed by Thomas Shenk

Abstract

Recently, several proteins have been identified that are related in their sequence to the p53 tumor-suppressor protein. One of these proteins, which is termed p73, exhibits sequence homology to the p53 transcriptional activation, DNA binding, and oligomerization domains. The adenovirus E1B 55-kDa protein, the adenovirus E4orf6 protein, and SV40 T antigen each can bind to p53 and inhibit p53 function. Here we demonstrate that the adenovirus E4orf6 protein, but not the E1B 55-kDa protein or T antigen, interacts with p73. The E4orf6 protein inhibits p73-mediated transcriptional activation and cell killing in a manner similar to its effect on p53. Thus, only a subset of viral oncoproteins that antagonize p53 function also interacts with the related p73 protein.

Footnotes

  • Present address: Department of Oral Pathology, Hokkaido University School of Dentistry, N13 W7, Kita-ku Sapporo 060-0813, Japan.

  • § To whom reprint requests should be addressed. e-mail: tshenk{at}princeton.edu.

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