Reactome | CFTR binds components of the ERAD machinery for ubiquitination and degradation

CFTR binds components of the ERAD machinery for ubiquitination and degradation

Stable Identifier

R-HSA-8866551

Type

Reaction [binding]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane

ReviewStatus

5/5

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CFTR binds components of the ERAD machinery for ubiquitination and degradation

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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