Repression of bax gene expression by the HTLV-1 Tax protein: implications for suppression of apoptosis in virally infected cells.

The human T-cell leukemia virus-encoded oncoprotein Tax is a potent deregulator of cellular gene expression. Here we report that Tax represses transcription of the human bax gene, a gene whose protein product accelerates apoptosis. This repression is mediated through a 27-bp sequence in the bax promoter that contains a putative basic helix-loop-helix binding site. Deletion of this sequence abolishes Tax-mediated repression of bax. Repression of the bax gene may be biologically significant, as we also show that HTLV-I-infected cell lines are resistant to a variety of physical, chemical, and biological stimuli which induce apoptosis in uninfected T-cells. The repression of genes involved in promoting apoptosis, including the bax gene, may contribute to retroviral survival, and initiate a pathway toward malignant transformation.