Transrepression of RNA polymerase II promoters by the simian virus 40 small t antigen

Simian virus 40 (SV40) small t antigen (t) can activate transcription from certain RNA polymerase II and III promoters (M. Loeken, I. Bikel, D. M. Livingston, and J. Brady, Cell 55:1171-1177, 1988). Here we report a new function of t, its ability to repress human c-fos promoter and AP-1 transcriptional activity in CV-1P cells. This function is the product of a discrete N-terminal domain of t, because the large T antigen (T)/t-common polypeptide, which contains only the first 82 amino acids common to both T and t of SV40, was, like the intact protein, an active repressor. The data further suggest that the t- and T/t-common-mediated repression of c-fos expression was most likely manifest at the level of transcription. In keeping with the possibility that t affects the expression of the genomic c-fos promoter, it also led to repression of AP-1 formation. Thus, SV40 is both an activator and a repressor of transcription. Its ability to inhibit c-fos expression should be considered in light of the natural history of SV40 in its natural host.