Up to two thirds of wild-type CFTR is targeted for co-translational degradation by the ERAD pathway due to inefficient folding (Jensen et al, 1995; Ward et al, 1994; Ward et al, 1995; Gelman et al, 2002; Lukacs et al, 1994). Misfolded CFTR is ubiquitinated in the ER by E3 ligases RNF5 and RNF185, likely as part of a mulitprotein retrotranslocation complex containing the hexameric ATPase VCP and various scaffolding and structural proteins (reviewed in Vembar and Brodsky, 2008). Consistent with this, RNF185 interacts directly both with CFTR and with other components of the ERAD machinery, including E2 proteins, ERLIN and DERLIN proteins (Younger et al, 2006; El Khouri et al, 2013).
El Khouri, E, Toledano, MB, Le Pavec, G, Delaunay-Moisan, A
Omura, S, Ward, CL, Kopito, RR
Fan, CY, Ren, HY, Rosser, MF, Younger, JM, Cyr, DM, Turnbull, EL, Chen, L, Patterson, C
Ward, CL, Kopito, RR
Kannegaard, ES, Kopito, RR, Gelman, MS
Jensen, TJ, Loo, MA, Williams, DB, Riordan, JR, Pind, S, Goldberg, AL
Chang, XB, Lukacs, GL, Grinstein, S, Riordan, JR, Mohamed, A, Kartner, N
Vembar, SS, Brodsky, JL
Hodson, M, Santis, G, Knight, R, Osborne, L
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