What question did this study set out to answer?

To determine whether Derlin-1 and p97 mediate the endoplasmic reticulum-associated degradation of wild-type CFTR and its disease-associated folding mutants.

September 6, 2006Journal of Biological ChemistryOpen Access

Derlin-1 Promotes the Efficient Degradation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and CFTR Folding Mutants

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Authors

FSFei SunUniversity of California, Los Angeles RZRuilin ZhangWuhan University XGXiaoyan GongShanxi Medical University

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Implication

Laboratory study reveals Derlin-1 coordinates degradation of mutant CFTR in airway epithelial cells, suggesting its role in early surveillance during channel biogenesis.

Key Points

To determine whether Derlin-1 and p97 mediate the endoplasmic reticulum-associated degradation of wild-type CFTR and its disease-associated folding mutants.
Examined protein-protein interactions and intracellular localization of Derlin-1, p97, and CFTR in human airway epithelial cells.
Assessed CFTR turnover, aggregate accumulation, and domain-specific degradation using exogenous Derlin-1 expression, truncated CFTR fragments, and ~70% Derlin-1 knockdown via RNA interference.
Derlin-1 selectively bound nonubiquitylated CFTR, while p97 interacted with ubiquitylated CFTR; exogenous Derlin-1 degraded >90% of folding mutants (DeltaF508 and G85E) and reduced insoluble aggregates.
Endogenous Derlin-1 knockdown of ~70% increased steady-state levels of both wild-type and DeltaF508 CFTR by 10- to 15-fold.
Derlin-1 primarily mediated the degradation of N-terminal fragments encompassing the first transmembrane domain, with reduced efficiency on fragments containing downstream domains.

Cite This Study

Sun et al. (2006) studied this question.

synapsesocial.com/papers/6a8c33f1c12eaf65c8b23742 https://doi.org/10.1074/jbc.m607085200

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Implication

Laboratory study reveals Derlin-1 coordinates degradation of mutant CFTR in airway epithelial cells, suggesting its role in early surveillance during channel biogenesis.

Derlin-1 Promotes the Efficient Degradation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and CFTR Folding Mutants

Discussion

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Implication

Key Points

Cite This Study

Derlin-1 Promotes the Efficient Degradation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and CFTR Folding Mutants

Discussion

Member takes

Implication

Key Points

Cite This Study

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