Viral Oncoproteins Discriminate between p53 and the p53 Homolog p73

Author:

Marin Maria Carmen1,Jost Christine A.1,Irwin Meredith S.1,DeCaprio James A.1,Caput Daniel2,Kaelin William G.13

Affiliation:

1. Dana-Farber Cancer Institute and Harvard Medical School 1 and

2. Sanofi Recherche, Labege, France2

3. Howard Hughes Medical Institute, 3 Boston, Massachusetts 02115, and

Abstract

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.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

Reference53 articles.

1. Enhanced degradation of p53 protein in HPV-E6 and BPV-1 E6 immortalized human mammary epithelial cells;Band V.;EMBO J.,1993

2. A proteolytic fragment from the central region of p53 has marked sequence-specific DNA-binding activity when generated from wild-type but not oncogenic mutant p53 protein;Bargonetti J.;Genes Dev.,1993

3. Site-specific binding of wild-type p53 to cellular DNA is inhibited by SV40 T antigen and mutant p53;Bargonetti J.;Genes Dev.,1992

4. Adenovirus E1b-58 kD antigen binds to p53 during infection of rodent cells: evidence for an N-terminal binding site on p53;Braithwaite A. W.;Oncogene,1991

5. Caput D. Unpublished data.

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