The mechanism of trans-activation of the MDR1 gene by human T-cell leukemia virus.

Abstract

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.

• Authors: A Lau, T W Gant, A J Cann
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 249 Issue 2 Pg. 397-404 (Aug 19 1998) ISSN: 0006-291X [Print] United States
• PMID: 9712708 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 1998 Academic Press.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Adaptor Protein Complex alpha Subunits
• Adaptor Proteins, Vesicular Transport
• CCAAT-Enhancer-Binding Proteins
• DNA-Binding Proteins
• Gene Products, tax
• Membrane Proteins
• Nuclear Proteins

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Adaptor Protein Complex alpha Subunits
• Adaptor Proteins, Vesicular Transport
• Animals
• Binding Sites
• CCAAT-Enhancer-Binding Proteins
• COS Cells
• DNA-Binding Proteins (metabolism)
• Gene Deletion
• Gene Expression
• Gene Products, tax (pharmacology)
• Genes, MDR (genetics)
• Human T-lymphotropic virus 1 (physiology)
• Membrane Proteins (metabolism)
• Mutagenesis, Site-Directed
• Nuclear Proteins (metabolism)
• Promoter Regions, Genetic
• Transcription, Genetic (drug effects)
• Transcriptional Activation