| Derlin 1 serves to retain CFTR in the ER membrane and interacts with RMA 1 and Ubc6e to promote CFTR ' s proteasomal degradation . ^^^ RMA 1 is capable of recognizing folding defects in CFTR Delta F 508 coincident with translation , whereas the CHIP E 3 appears to act posttranslationally . ^^^ A folding defect in CFTR Delta F 508 detected by RMA 1 involves the inability of CFTR ' s second membrane spanning domain to productively interact with amino terminal domains . ^^^ Thus , the RMA 1 and CHIP E 3 ubiquitin ligases act sequentially in ER membrane and cytosol to monitor the folding status of CFTR and CFTR Delta F508 . . ^^^ |