There is growing evidence that abnormal protein folding or trafficking (protein kinesis) leads
to diseases. We have used P-glycoprotein as a model protein to develop strategies to
overcome defects in protein kinesis. Misprocessed mutants of the human P-glycoprotein are
retained in the endoplasmic reticulum as core-glycosylated biosynthetic intermediates and
rapidly degraded. Synthesis of the mutant proteins in the presence of drug substrates or
modulators such as capsaicin, cyclosporin, vinblastine, or verapamil, however, resulted in …