Proteasomal Targeting of CFTR 3
Class II mutations of CFTR, such as DF508, are categorized based on a defect in protein trafficking and degradation. DF508 is found in 90% of patients with cystic fibrosis in the United States, and this mutation results in a partially functional chloride channel that is degraded before it reaches the plasma membrane. The degradation vs. maturation decision is thought to involve a large number of proteins including chaperones, ERAD machinery proteins, and ubiquitin pathway proteins. The identification of novel members of the CFTR proteasomal targeting machinery will be essential to the understanding of CF biology as well as the development of effective therapeutic targets, and we will attempt to identify and characterize several of these molecules.