CFTR binds components of the ERAD machinery for ubiquitination and degradation

Stable Identifier
Reaction [binding]
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
24019521 RNF185 is a novel E3 ligase of endoplasmic reticulum-associated degradation (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR)

El Khouri, E, Toledano, MB, Le Pavec, G, Delaunay-Moisan, A

J. Biol. Chem. 2013
7553863 Degradation of CFTR by the ubiquitin-proteasome pathway

Omura, S, Ward, CL, Kopito, RR

Cell 1995
16901789 Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator

Fan, CY, Ren, HY, Rosser, MF, Younger, JM, Cyr, DM, Turnbull, EL, Chen, L, Patterson, C

Cell 2006
7523390 Intracellular turnover of cystic fibrosis transmembrane conductance regulator. Inefficient processing and rapid degradation of wild-type and mutant proteins

Ward, CL, Kopito, RR

J. Biol. Chem. 1994
11812794 A principal role for the proteasome in endoplasmic reticulum-associated degradation of misfolded intracellular cystic fibrosis transmembrane conductance regulator

Kannegaard, ES, Kopito, RR, Gelman, MS

J. Biol. Chem. 2002
7553864 Multiple proteolytic systems, including the proteasome, contribute to CFTR processing

Jensen, TJ, Loo, MA, Williams, DB, Riordan, JR, Pind, S, Goldberg, AL

Cell 1995
7529176 Conformational maturation of CFTR but not its mutant counterpart (delta F508) occurs in the endoplasmic reticulum and requires ATP

Chang, XB, Lukacs, GL, Grinstein, S, Riordan, JR, Mohamed, A, Kartner, N

EMBO J. 1994
19002207 One step at a time: endoplasmic reticulum-associated degradation

Vembar, SS, Brodsky, JL

Nat. Rev. Mol. Cell Biol. 2008
1998343 A mutation in the second nucleotide binding fold of the cystic fibrosis gene

Hodson, M, Santis, G, Knight, R, Osborne, L

Am. J. Hum. Genet. 1991
Orthologous Events
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