HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX PROTEIN REPRESSES GENE-EXPRESSION THROUGH THE BASIC HELIX-LOOP-HELIX FAMILY OF TRANSCRIPTION FACTORS

The human T-cell leukemia virus type I (HTLV-I) oncoprotein Tax is a p otent activator of viral and cellular gene transcription. Tax does not bind DNA directly but utilizes cellular transcription factors to medi ate activation. In this report, we examine the role of the basic helix -loop-helix (bHLH) proteins in Tax deregulation of gene expression, as these proteins play a critical role in progression through the cell c ycle and have been implicated in neoplastic disease. We show that the bHLH proteins do not mediate activation, but instead mediate repressio n of gene expression in the presence of Tax. We further show that a co nsensus bHLH binding site in the promoter of the beta-polymerase gene, which encodes an enzyme involved in DNA repair, mediates the previous ly reported repression of beta-polymerase gene expression by Tax. Toge ther, these results suggest that Tax may induce malignant transformati on, at least in part, through bHLH-mediated repression of key cellular regulatory genes.