A 47-AMINO-ACID FRAGMENT OF SV40 T-ANTIGEN REPRESSES TRANSCRIPTION FROM HUMAN GST-ALPHA PROMOTERS

SV40 T antigen downregulates the expression of an important detoxifica tion enzyme, glutathione S-transferase alpha (GST alpha). We show here that the target of this repression is a 14-bp element common to the h uman 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, altho ugh the TAGR element does resemble the binding site for the [karos tra nscription factor found in hematopoietic cells. We also have identifie d a 47-amino-acid fragment of T antigen that includes amino acids 83-1 00 and 119-147, which is sufficient to repress transcription from the GST alpha promoter in transient transcription assays. Thus, GST alpha repression does not require binding of T antigen to pRb, p300, or p53, since the domains or T antigen required for binding these cellular pr oteins are missing from this T antigen fragment. We show, however, tha t this fragment does bind to three cellular proteins with approximate molecular weights of 54, 59, and 94 kDa. (C) 1998 Academic Press.