Binding of p300/CBP co-activators by polyoma large T antigen.
Small DNA tumor viruses such as simian virus 40 (SV40) and polyomavirus (Py) take advantage of host cell proteins to transcribe and replicate their DNA. Interactions between the viral T antigens and host proteins result in cell transformation and tumor induction. Large T antigen of SV40 interacts with p53, pRb/p107/p130 family members, and the cyclic AMP-responsive element-binding protein (CREB)-binding protein (CBP)/p300. Py large T antigen is known to interact only with pRb and p300 among these proteins. Here we report that Py large T binds to CBP in vivo and in vitro. In co-transfection assays, Py large T inhibits the co-activation functions of CBP/p300 in CREB-mediated transactivation but not in NF-kappa B-mediated transactivation. p53 appears not to be involved in the functions of CREB-mediated transactivation and is not essential for large T:CBP interaction. Mutations introduced into a region of Py large T with homology to adenovirus E1A and SV40 large T prevent binding to the co-activators. These mutant large T antigens fail to inhibit CREB-mediated transactivation. The CBP/p300-binding Py mutants are able to transform established rat embryo fibroblasts but are restricted in their ability to induce tumors in the newborn mouse, indicating that interaction of large T with the co-activators may be essential for virus replication and spread in the intact host.
Cho
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Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Tian
Y
Y
Benjamin
T L
TL
D016475:3T3 Cells; D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002478:Cells, Cultured; D050881:E1A-Associated p300 Protein; D005347:Fibroblasts / Q000378:metabolism; D016158:Genes, p53 / Q000235:genetics; D005982:Glutathione Transferase / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D017500:Adenovirus E1A Proteins; D000952:Antigens, Polyomavirus Transforming; D016328:NF-kappa B; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; C494362:Ep300 protein, rat; D005982:Glutathione Transferase