Evidence map›Paper›PMID 29503157›Full record

ArticleDevelopmental cell2018

Chaperone-Independent Peripheral Quality Control of CFTR by RFFL E3 Ligase.

Tsukasa Okiyoneda, Guido Veit, Ryohei Sakai, Misaki Aki, Takeshi Fujihara, Momoko Higashi, Seiko Susuki-Miyata, Masanori Miyata, Norihito Fukuda, Akihiko Yoshida and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Developmental cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
6.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 79 citations in OpenAlex.

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  18. Targeting ubiquitination machinery in cystic fibrosis: Where do we stand?Cellular and molecular life sciences : CMLS · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 2 countries.

Tsukasa OkiyonedaDepartment of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan; Department of Physiology, McGill University, 3655 Promenade Sir-William-Osler, Montréal, QC H3G 1Y6, Canada. Electronic address: t-okiyoneda@kwansei.ac.jp.
Guido VeitDepartment of Physiology, McGill University, 3655 Promenade Sir-William-Osler, Montréal, QC H3G 1Y6, Canada.
Ryohei SakaiDepartment of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan.
Misaki AkiDepartment of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan.
Takeshi FujiharaDepartment of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan.
Momoko HigashiDepartment of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan.
Seiko Susuki-MiyataDepartment of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan.
Masanori MiyataDepartment of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan.
Norihito FukudaDepartment of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan.
Akihiko YoshidaDepartment of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan.
Haijin XuDepartment of Physiology, McGill University, 3655 Promenade Sir-William-Osler, Montréal, QC H3G 1Y6, Canada.
Pirjo M ApajaDepartment of Physiology, McGill University, 3655 Promenade Sir-William-Osler, Montréal, QC H3G 1Y6, Canada.
Gergely L LukacsDepartment of Physiology, McGill University, 3655 Promenade Sir-William-Osler, Montréal, QC H3G 1Y6, Canada; Department of Biochemistry, McGill University, Montréal, QC H3G 1Y6, Canada; Department of GRASP, McGill University, Montréal, QC H3G 1Y6, Canada. Electronic address: gergely.lukacs@mcgill.ca.
Kwansei Gakuin University · JPMcGill University · CA

Funding

Correction of defective functional expression of CFTR in cystic fibrosisR01DK075302 · NIDDK · MCGILL UNIVERSITY · PI LUKACS, GERGELY L. · 2006 to 2020
$3.3M
CIHRNIDDK NIH HHS R01 DK075302
6 · The paper itself

Abstract

The peripheral protein quality control (QC) system removes non-native membrane proteins, including ΔF508-CFTR, the most common CFTR mutant in cystic fibrosis (CF), from the plasma membrane (PM) for lysosomal degradation by ubiquitination. It remains unclear how unfolded membrane proteins are recognized and targeted for ubiquitination and how they are removed from the apical PM. Using comprehensive siRNA screens, we identified RFFL, an E3 ubiquitin (Ub) ligase that directly and selectively recognizes unfolded ΔF508-CFTR through its disordered regions. RFFL retrieves the unfolded CFTR from the PM for lysosomal degradation by chaperone-independent K63-linked poly-ubiquitination. RFFL ablation enhanced the functional expression of cell-surface ΔF508-CFTR in the presence of folding corrector molecules, and this effect was further improved by inhibiting the Hsc70-dependent ubiquitination machinery. We propose that multiple peripheral QC mechanisms evolved to dispose of non-native PM proteins and to preserve cellular proteostasis, even at the cost of eliminating partially functional polypeptides.

Indexed as

Molecular ChaperonesCell MembraneCells, CulturedCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsGene Knockdown TechniquesHumansLysosomesMutationProteolysisRNA, Small InterferingUbiquitinUbiquitinationUbiquitin-Protein LigasesCFTR protein, humanCystic Fibrosis Transmembrane Conductance Regulatorcystic fibrosis transmembrane conductance regulator delta F508Molecular ChaperonesRNA, Small InterferingUbiquitinUbiquitin-Protein LigasesCFTRcystic fibrosisendosomeprotein quality controlubiquitination

Identifiers

PMID29503157
PMCPMC6447300
OpenAlexW2792910868

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.