Evidence map›Paper›PMID 30581143›Full record

ArticleMolecular cell2019

Genome-wide CRISPR Analysis Identifies Substrate-Specific Conjugation Modules in ER-Associated Degradation.

Dara E Leto, David W Morgens, Lichao Zhang, Christopher P Walczak, Joshua E Elias, Michael C Bassik, Ron R Kopito

Abstract read
In one paragraph

Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed
–field-weighted citation impact
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

88 citing papers in PubMed.

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28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Dara E LetoDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
David W MorgensDepartment of Genetics, Stanford University, Stanford, CA 94305, USA.
Lichao ZhangDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Christopher P WalczakDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Joshua E EliasDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Michael C BassikDepartment of Genetics, Stanford University, Stanford, CA 94305, USA; Program in Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA 94305, USA.
Ron R KopitoDepartment of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: kopito@stanford.edu.

Funding

The Ubiquitin Proteasome System in Quality ControlR01GM074874 · NIGMS · STANFORD UNIVERSITY · PI KOPITO, RON R · 2006 to 2022
$8.0M
Four Laser, 18 Color Cell Sorter in the SSFFS10RR025518 · NCRR · STANFORD UNIVERSITY · PI HERZENBERG, LEONARD A · 2009 to 2009
$500k
BD Canto II RUO CytometerS10RR027431 · NCRR · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2010 to 2010
$236k
Elucidating the architecture of native multiprotein complexes involved in ER-associated degradationF32GM113378 · NIGMS · STANFORD UNIVERSITY · PI WALCZAK, CHRISTOPHER PAUL · 2015 to 2017
$168k
Genetic interaction (GI) analysis of the mammalian ERAD systemF32GM113370 · NIGMS · STANFORD UNIVERSITY · PI LETO, DARA · 2015 to 2015
$58k
NCRR NIH HHS S10 RR025518NCRR NIH HHS S10 RR027431NIGMS NIH HHS F32 GM113370NIGMS NIH HHS F32 GM113378NIGMS NIH HHS R01 GM074874
6 · The paper itself

Abstract

The ubiquitin proteasome system (UPS) maintains the integrity of the proteome by selectively degrading misfolded or mis-assembled proteins, but the rules that govern how conformationally defective proteins in the secretory pathway are selected from the structurally and topologically diverse constellation of correctly folded membrane and secretory proteins for efficient degradation by cytosolic proteasomes is not well understood. Here, we combine parallel pooled genome-wide CRISPR-Cas9 forward genetic screening with a highly quantitative and sensitive protein turnover assay to discover a previously undescribed collaboration between membrane-embedded cytoplasmic ubiquitin E3 ligases to conjugate heterotypic branched or mixed ubiquitin (Ub) chains on substrates of endoplasmic-reticulum-associated degradation (ERAD). These findings demonstrate that parallel CRISPR analysis can be used to deconvolve highly complex cell biological processes and identify new biochemical pathways in protein quality control.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsEndoplasmic Reticulum-Associated DegradationProteostasisCRISPR-Associated Protein 9Genome-Wide Association StudyHEK293 CellsHumansK562 CellsKineticsProteasome Endopeptidase ComplexProtein FoldingProteolysisRicinSubstrate SpecificityUbiquitinationCRISPR-Associated Protein 9Proteasome Endopeptidase ComplexRicinSYVN1 protein, humanUbiquitin-Protein Ligases

Identifiers

PMID30581143
PMCPMC6338494

What OpenQuestion holds

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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.