Evidence map›Paper›PMID 33523898›Full record

ArticleScience advances2021

The translocon-associated protein (TRAP) complex regulates quality control of N-linked glycosylation during ER stress.

Chatchai Phoomak, Wei Cui, Thomas J Hayman, Seok-Ho Yu, Peng Zhao, Lance Wells, Richard Steet, Joseph N Contessa

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

27 citing papers in PubMed, 47 citations in OpenAlex.

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  15. Food & function · 2024
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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

8 authors at 3 institutions in 1 country.

Chatchai PhoomakDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-3808-8816
Wei CuiDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Thomas J HaymanDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Seok-Ho YuGreenwood Genetic Center, Greenwood, SC 29646, USA.
Peng ZhaoComplex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30601, USA.ORCID 0000-0002-9296-5293
Lance WellsComplex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30601, USA.ORCID 0000-0003-4956-5363
Richard SteetGreenwood Genetic Center, Greenwood, SC 29646, USA.
Joseph N ContessaDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510, USA. joseph.contessa@yale.edu.ORCID 0000-0001-9408-1865
Yale University · USGreenwood Genetic Center · USUniversity of Georgia · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
PATHOGENIC MECHANISMS OF LYSOSOMAL DISEASER01GM086524 · NIGMS · UNIVERSITY OF GEORGIA · PI STEET, RICHARD · 2009 to 2021
$4.0M
Origin of N-Glycan Site-Specific HeterogeneityR01GM130915 · NIGMS · UNIVERSITY OF GEORGIA · PI KANNAN, NATARAJAN, MOREMEN, KELLEY W. · 2019 to 2022
$3.4M
OST Inhibition in NSCLCR01CA240418 · NCI · YALE UNIVERSITY · PI CONTESSA, JOSEPH N · 2020 to 2024
$2.4M
Regulation of N-linked glycosylation in Mammalian CellsR01GM127383 · NIGMS · YALE UNIVERSITY · PI CONTESSA, JOSEPH N · 2018 to 2019
$659k
NCATS NIH HHS UL1 TR001863NCI NIH HHS R01 CA240418NIGMS NIH HHS R01 GM086524NIGMS NIH HHS R01 GM127383NIGMS NIH HHS R01 GM130915
6 · The paper itself

Abstract

Asparagine (N)-linked glycosylation is required for endoplasmic reticulum (ER) homeostasis, but how this co- and posttranslational modification is maintained during ER stress is unknown. Here, we introduce a fluorescence-based strategy to detect aberrant N-glycosylation in individual cells and identify a regulatory role for the heterotetrameric translocon-associated protein (TRAP) complex. Unexpectedly, cells with knockout of SSR3 or SSR4 subunits restore N-glycosylation over time concurrent with a diminished ER stress transcriptional signature. Activation of ER stress or silencing of the ER chaperone BiP exacerbates or rescues the glycosylation defects, respectively, indicating that SSR3 and SSR4 enable N-glycosylation during ER stress. Protein levels of the SSR3 subunit are ER stress and UBE2J1 dependent, revealing a mechanism that coordinates upstream N-glycosylation proficiency with downstream ER-associated degradation and proteostasis. The fidelity of N-glycosylation is not static in both nontransformed and tumor cells, and the TRAP complex regulates ER glycoprotein quality control under conditions of stress.

Identifiers

PMID33523898
PMCPMC7810369
OpenAlexW3122519595

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

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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.