SV40 T antigen abrogates p53-mediated transcriptional activity.
Recent evidence suggests that the tumor-suppressor protein p53 functions as a transcriptional regulator to control cell proliferation. An interaction with p53 is required for SV40 T antigen to transform primary cells; however, the effect of T antigen binding on p53 function is not known. In order to determine if an interaction with T antigen results in loss of p53-mediated transcriptional activity, we have used vectors expressing either a p53-GAL4 fusion protein or a wild-type p53 protein in transient co-transfection assays with T-antigen expression vectors. We have demonstrated that coexpression of T antigen significantly reduces both p53-GAL4-mediated transcription from a GAL4-dependent CAT reporter and p53-mediated transcription from a consensus p53 binding site in vivo. Moreover, T antigen was able to reduce binding of p53-GAL4 to its GAL4 binding sequence in gel shift experiments in vitro. These observed activities of T antigen were all dependent upon a functional p53-binding domain. In addition, coexpression of human papillomavirus type 18 E6 protein, able to bind to p53, was able to significantly reduce p53-mediated transcription. These results suggest that an interaction of certain viral oncoproteins with p53 results in loss of transcriptional activity of p53, a function that is important for maintaining normal cell growth.
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261.
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D
Jiang
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Srinivasan
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G
Lozano
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Robbins
D016475:3T3 Cells; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000494:pharmacology*; D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005656:Fungal Proteins / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000187:drug effects*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology
D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004247:DNA