HTLV-1 ONCOPROTEIN TAX DEREGULATES TRANSCRIPTION OF CELLULAR GENES THROUGH MULTIPLE MECHANISMS

Infection of a human retrovirus HTLV-1 induces adult T cell leukemia and a neurological disease, HAM/TSP. Regulatory protein Tax of HTLV-1 is thought to contribute to the pathogenesis. We have studied the mechanism of transcriptional activation induced by Tax protein and identified two independent mechanisms: (a) binding to the enhancer-binding proteins, CREB, CREM, NF-kappa B and SRF, resulting in the activation of these factors through indirect binding to each specific DNA sequence, and (b) binding to I kappa B protein resulting in the suppression of the negative regulator I kappa B, which binds to NF-kappa B. In addition to these factors, a new protein GLI/THP is also involved in the transactivation. On the basis of these mechanisms, gene regulations in vitro and in vivo in HTLV-1-infected cells are discussed.