Deletion of phenylalanine 508 in CFTR is the most prevalent mutation causing cystic fibrosis (Riordan et al, 1989; Kerem et al, 1989). F508 deletion causes destabilization and subsequent targeting for co-translational degradation by the ER-associated degradation machinery (ERAD). Like misfolded WT CFTR protein, F508del is ubiquitinated by ERAD-associated E3 ligases including RNF5 and RNF 185, targeting it for VCP-mediated retrotranslocation and 26S proteasomal degradation (Meachem et al, 2001; Rosser et al, 2008; Younger et al, 2004; Younger et al, 2006; El Khouri et al, 2013; reviewed in Pranke and Sermet-Gaudelus, 2014).
El Khouri, E, Toledano, MB, Le Pavec, G, Delaunay-Moisan, A
Fields, A, Fan, CY, Ren, HY, Younger, JM, Cyr, DM, Chen, L, Patterson, C
Fan, CY, Ren, HY, Rosser, MF, Younger, JM, Cyr, DM, Turnbull, EL, Chen, L, Patterson, C
Grove, DE, Rosser, MF, Cyr, DM, Chen, L
Chou, JL, Alon, N, Kerem, B, Riordan, JR, Rozmahel, R, Plavsic, N, Grzelczak, Z, Lok, S, Zielenski, J, Rommens, JM
Meacham, GC, Younger, JM, Zhang, W, Cyr, DM, Patterson, C
Sermet-Gaudelus, I, Pranke, IM
Markiewicz, D, Buchanan, JA, Buchwald, M, Kerem, B, Cox, TK, Tsui, LC, Chakravarti, A, Rommens, JM
Gain of function of CFTR F508del [endoplasmic reticulum membrane]
© 2023 Reactome