A 47-amino-acid fragment of SV40 T antigen represses transcription from human GSTalpha promoters.
SV40 T antigen downregulates the expression of an important detoxification enzyme, glutathione S-transferase alpha (GSTalpha). We show here that the target of this repression is a 14-bp element common to the human GSTA1 and GSTA2 promoters. This element, which we have named TAGR, is also critical for high-level, constitutive expression from these promoters. The TAGR element does not appear to contain a binding site for any transcription factor known to be present in fibroblasts, although the TAGR element does resemble the binding site for the Ikaros transcription factor found in hematopoietic cells. We also have identified a 47-amino-acid fragment of T antigen that includes amino acids 83-100 and 119-147, which is sufficient to repress transcription from the GSTalpha promoter in transient transcription assays. Thus, GSTalpha repression does not require binding of T antigen to pRb, p300, or p53, since the domains of T antigen required for binding these cellular proteins are missing from this T antigen fragment. We show, however, that this fragment does bind to three cellular proteins with approximate molecular weights of 54, 59, and 94 kDa.
Sompayrac
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Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado, 80309, USA. laurens@Alum.mit.edu
Jane
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Lörper
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Sies
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D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D051740:Ikaros Transcription Factor; D010446:Peptide Fragments / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013539:Simian virus 40 / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051740:Ikaros Transcription Factor; D004247:DNA; D005982:Glutathione Transferase