Modulators of the ABC transporter family and methods for their use
An isolated factor derived from the bacterium Pseudomonas aeruginosa and confirmed by proteomics to be a protein that reduces expression of ABC transmembrane proteins and active fragments and mimetics thereof are provided. Also provided is a method for inhibiting expression of ABC transmembrane proteins in cells by administering to the cells the isolated factor or protein or active fragment thereof or a mimetic thereof. Such methods are useful in the enhancing delivery of small molecule therapeutic agents to the CNS and in treating cancers, particularly multidrug resistant cancers, and secretory diarrhea. In addition, compositions, methods for identifying compositions and methods for use of compositions that inhibit suppression of ABC transmembrane protein expression or reduce epoxide hydrolase activity by this factor are provided. Such compositions and methods are useful in treatment of cystic fibrosis.
1. A method for modulating plasma membrane expression of an ATP-binding cassette (ABC) transmembrane protein in a cell comprising administering to the cell a composition that modulates plasma membrane expression of ABC transmembrane protein, said composition comprising:
(a) a cystic fibrosis transmembrane conductance regulator inhibitory factor protein of SEQ ID NO:1 or fragment of SEQ ID NO:1 which exhibits the same or similar plasma membrane expression of the ABC transmembrane protein modulating activity as SEQ ID NO:1; and
(b) a physiologically acceptable vehicle.
2. The method of claim 1 wherein the cell is a mammalian cell.
3. The method of claim 1 wherein the composition comprises the cystic fibrosis transmembrane conductance regulator inhibitory factor protein of SEQ ID NO:1.