TRANSCRIPTIONAL REPRESSION OF P53 BY HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX PROTEIN

The human T-cell leukemia virus type I oncoprotein Tax transcriptional ly deregulates a wide variety of viral and cellular genes. Tax deregul ation of gene expression is mediated through interaction with a variet y of structurally unrelated cellular transcription factors, as Tax doe s not bind DNA in a sequence-specific manner. Although most of these c ellular transcription factors have been shown to mediate activation by Tax, we have recently demonstrated that members of the basic helix-lo op-helix (bHLH) family of transcription factors, which play a critical role in progression through the cell cycle, mediate repression by Tax . In this report, we examined whether Tax might repress transcription of the tumor suppressor p53, as the p53 gene has recently been demonst rated to be regulated by the bHLH protein c-Myc. Furthermore, loss or inactivation of the p53 gene has been shown to be causally associated with oncogenic transformation. We show that Tax represses transcriptio n of the p53 gene and that this repression is dependent upon the bHLH recognition element in the p53 promoter. Together, these results sugge st that Tax may promote malignant transformation through repression of p53 transcription.