THE POU DOMAIN PROTEIN TST-1 AND PAPOVAVIRAL LARGE TUMOR-ANTIGEN FUNCTION SYNERGISTICALLY TO STIMULATE GLIA-SPECIFIC GENE-EXPRESSION OF JC VIRUS

Synergism between transcriptional activators is a powerful way of pote ntiating their function. Here we show that the glial POU domain protei n Tst-1 (also known as Oct-6 and SCIP) and large tumor antigen (T anti gen) synergistically increased transcription from both the early and t he late promoters of papovavirus JC in glial cells. Synergism between both proteins did not require T-antigen-mediated DNA replication or di rect binding of T antigen to the promoter. The ability of T antigen to functionally cooperate with Tst-1 was contained within its N-terminal region, shown by the fact that small tumor antigen (t antigen) could substitute for T antigen in transfection experiments. In addition to t his functional synergism, a direct interaction between Tst-1 and T ant igen was observed in vitro. Using deletion mutants of Tst-1 and T anti gen, the POU domain of Tst-1 and the N-terminal region of T antigen we re found to participate in this interaction. Because of the low levels of Tst-1 present in oligodendrocytes, synergism between Tst-1 and T a ntigen could be an important factor in establishing the lytic infectio n of oligodendrocytes by JC virus during the course of the fatal demye linating disease progressive multifocal leukoencephalopathy.