Evidence map›Paper›PMID 29851562›Full record

ArticleMolecular biology of the cell2018

Dynamic changes in complexes of IRE1α, PERK, and ATF6α during endoplasmic reticulum stress.

Arunkumar Sundaram, Suhila Appathurai, Rachel Plumb, Malaiyalam Mariappan

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

52 citing papers in PubMed, 80 citations in OpenAlex.

  1. Review
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  4. Cell surface GRP78 and the UPR pathway as novel promising therapeutic targets in cancer: an insight into the treatment of acute leukemia by using GRP78-CART cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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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

4 authors at 1 institution in 1 country.

Arunkumar SundaramDepartment of Cell Biology, Nanobiology Institute, Yale School of Medicine, West Haven, CT 06516.
Suhila AppathuraiDepartment of Cell Biology, Nanobiology Institute, Yale School of Medicine, West Haven, CT 06516.
Rachel PlumbDepartment of Cell Biology, Nanobiology Institute, Yale School of Medicine, West Haven, CT 06516.
Malaiyalam MariappanDepartment of Cell Biology, Nanobiology Institute, Yale School of Medicine, West Haven, CT 06516.
Yale University · US

Funding

The mechanism of Ire1-mediated mRNA cleavage during endoplasmic reticulum stressR01GM117386 · NIGMS · YALE UNIVERSITY · PI MARIAPPAN, MALAIYALAM · 2016 to 2024
$3.0M
NIGMS NIH HHS R01 GM117386
6 · The paper itself

Abstract

The endoplasmic reticulum (ER) localized unfolded protein response (UPR) sensors, IRE1α, PERK, and ATF6α, are activated by the accumulation of misfolded proteins in the ER. It is unclear how the endogenous UPR sensors are regulated by both ER stress and the ER luminal chaperone BiP, which is a negative regulator of UPR sensors. Here we simultaneously examined the changes in the endogenous complexes of UPR sensors by blue native PAGE immunoblotting in unstressed and stressed cells. We found that all three UPR sensors exist as preformed complexes even in unstressed cells. While PERK complexes shift to large complexes, ATF6α complexes are reduced to smaller complexes on ER stress. In contrast, IRE1α complexes were not significantly increased in size on ER stress, unless IRE1α is overexpressed. Surprisingly, depletion of BiP had little impact on the endogenous complexes of UPR sensors. In addition, overexpression of BiP did not significantly affect UPR complexes, but suppressed ER stress mediated activation of IRE1α, ATF6α and, to a lesser extent, PERK. Furthermore, we captured the interaction between IRE1α and misfolded secretory proteins in cells, which suggests that the binding of unfolded proteins to preformed complexes of UPR sensors may be crucial for activation.

Indexed as

Endoplasmic Reticulum StressActivating Transcription Factor 6alpha 1-AntitrypsineIF-2 KinaseEndoplasmic Reticulum Chaperone BiPEndoribonucleasesHeat-Shock ProteinsHEK293 CellsHumansMultiprotein ComplexesMutationProtein BindingProtein FoldingProtein MultimerizationProtein Serine-Threonine KinasesUnfolded Protein ResponseActivating Transcription Factor 6alpha 1-AntitrypsinATF6 protein, humaneIF-2 KinaseEndoplasmic Reticulum Chaperone BiPEndoribonucleasesERN1 protein, humanHeat-Shock ProteinsMultiprotein ComplexesProtein Serine-Threonine Kinases

Identifiers

PMID29851562
PMCPMC5994896
OpenAlexW2801790428

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.