THE MECHANISM OF TRANSACTIVATION OF THE MDR1 GENE BY HUMAN T-CELL LEUKEMIA-VIRUS

Overexpression of P-glycoprotein (P-gp), the protein product of the mu ltidrug resistance gene (MDR1), confers a drug resistant phenotype on cells. We have recently demonstrated that the MDR1 promoter is transcr iptionally activated by the HTLV-I tax protein, providing an explanati on for the development of drug resistance in HTLV-I infections. Here w e report that HTLV-I mediated MDR1 activation is dependent on the pres ence of an NF-IL6-binding site located between base pairs -148 and -14 1 relative to the transcription start site. This finding opens up the possibility of moderating P-gp expression through interference with NF -IL6 binding to its trans recognition element and subsequent repressio n of MDR1 transcription. (C) 1998 Academic Press.