The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation

摘要: The folding of both wild-type and mutant forms the cystic-fibrosis transmembrane-conductance regulator (CFTR), a plasma-membrane chloride-ion channel, is inefficient. Most nascent CFTR retained in endoplasmic reticulum degraded by ubiquitin proteasome pathway. Aberrant defective trafficking CFTRDeltaF508 principal cause cystic fibrosis, but how endoplasmic-reticulum quality-control system targets for degradation remains unknown. CHIP cytosolic U-box protein that interacts with Hsc70 through set tetratricorepeat motifs. represents modified form ring-finger motif found ligases defines E4 family polyubiquitination factors. Here we show functions to sense folded state aberrant proteasomal promoting their ubiquitination. appeared essential this process because overexpresion CHIPDeltaU-box inhibited action endogenous blocked ubiquitination degradation. co-chaperone converts from protein-folding machine into factor quality control.