Lau A, Gant T W, Cann A J
Wellcome/CRC Institute, Tennis Court Road, Cambridge, CB2 1QR, United Kingdom.
Biochem Biophys Res Commun. 1998 Aug 19;249(2):397-404. doi: 10.1006/bbrc.1998.9142.
Overexpression of P-glycoprotein (P-gp), the protein product of the multidrug resistance gene (MDR1), confers a drug resistant phenotype on cells. We have recently demonstrated that the MDR1 promoter is transcriptionally activated by the HTLV-I tax protein, providing an explanation for the development of drug resistance in HTLV-I infections. Here we report that HTLV-I mediated MDR1 activation is dependent on the presence of an NF-IL6-binding site located between base pairs -148 and -141 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 repression of MDR1 transcription.
