Surface expression of the cystic fibrosis transmembrane conductance regulator mutant Delta F508 is markedly upregulated by combination treatment withsodium butyrate and low temperature

The Delta F508 gene mutation prevents delivery of the cystic fibrosis trans membrane conductance regulator (CFTR) to the plasma membrane. The current s tudy examines the biochemical basis for the upregulation of Delta F508 CFTR expression by sodium butyrate and low temperature. Surface CFTR protein ex pression was determined by quantitative immunoblot following surface biotin ylation and streptavidin extraction, CF gene expression was measured by Nor thern analysis and CFTR function by forskolin-stimulated I-125 efflux, Buty rate increased Delta F508 mRNA levels and protein expression but did not in crease the biochemical or functional expression of Delta F508 CFTR at the c ell surface. Low temperature increased the biochemical and functional expre ssion of Delta F508 CFTR at the cell. surface but did not increase CFTR mRN A levels. Combining treatments led to a synergistic increase in both Delta F508 mRNA and surface protein levels that results from the stabilization of CFTR mRNA and protein by low temperature. These findings indicate that sur face expression of Delta F508 CFTR can be markedly enhanced by carefully se lected combination agents. (C) 2000 Academic Press.