Repression of Bax Gene Expression by the HTLV-I Tax Protein: Implications for Suppression of Apoptosis in Virally Infected Cells

Abstract

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 humanbaxgene, a gene whose protein product accelerates apoptosis. This repression is mediated through a 27-bp sequence in thebaxpromoter that contains a putative basic helix–loop–helix binding site. Deletion of this sequence abolishes Tax-mediated repression ofbax.Repression of thebaxgene 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 thebaxgene, may contribute to retroviral survival, and initiate a pathway toward malignant transformation.