Cystic fibrosis is caused by more than 1000 mutations, the most common being the DF508 mutation. These mutations have\r\nbeen divided into five classes [1], with DF508 CFTR in class II. Here we have studied the class V mutation A455E. We report\r\nthat the mature and immature bands of A455E are rapidly degraded primarily by proteasomes; the short protein half-life of\r\nthis mutant therefore resembles that of DF508 CFTR. A455E could be rescued by treatment of the cells with proteasome\r\ninhibitors. Furthermore, co-transfection of A455E with the truncation mutant D264 CFTR also rescued the mature C band,\r\nindicating that A455E can be rescued by transcomplementation. We found that D264 CFTR bound to A455E, forming a\r\nbimolecular complex. Treatment with the compound correctors C3 and C4 also rescued A455E. These results are significant\r\nbecause they show that although DF508 belongs to a different class than A455E, it can be rescued by the same strategies,\r\noffering therapeutic promise to patients with Class V mutations.
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