Evidence map›Paper›PMID 28380378›Full record

ArticleCell metabolism2017

Targeting ABL-IRE1α Signaling Spares ER-Stressed Pancreatic β Cells to Reverse Autoimmune Diabetes.

Shuhei Morita, S Armando Villalta, Hannah C Feldman, Ames C Register, Wendy Rosenthal, Ingeborg T Hoffmann-Petersen, Morvarid Mehdizadeh, Rajarshi Ghosh, Likun Wang, Kevin Colon-Negron and 5 more

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

Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 121 papers.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed
18.6field-weighted citation impact, top 1% 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

121 citing papers in PubMed, 179 citations in OpenAlex.

  1. Trial
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  3. Article
  4. Article
  5. Article
  6. Review
  7. New and emerging therapies in type 1 diabetes mellitus.The Journal of clinical investigation · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Are We Ready With Prevention for Type 1 Diabetes?Diabetes/metabolism research and reviews · 2025
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Shuhei MoritaDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Lung Biology Center, University of California, San Francisco, San Francisco, CA 94143, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
S Armando VillaltaDiabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA; Institute for Immunology, University of California, Irvine, Irvine, CA 92697, USA.
Hannah C FeldmanDepartment of Chemistry, University of Washington, Seattle, WA 98195, USA.
Ames C RegisterDepartment of Chemistry, University of Washington, Seattle, WA 98195, USA.
Wendy RosenthalDiabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Ingeborg T Hoffmann-PetersenDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Lung Biology Center, University of California, San Francisco, San Francisco, CA 94143, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Morvarid MehdizadehDiabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Rajarshi GhoshDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Lung Biology Center, University of California, San Francisco, San Francisco, CA 94143, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Likun WangDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Lung Biology Center, University of California, San Francisco, San Francisco, CA 94143, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Kevin Colon-NegronDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Lung Biology Center, University of California, San Francisco, San Francisco, CA 94143, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Rosa Meza-AcevedoDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Lung Biology Center, University of California, San Francisco, San Francisco, CA 94143, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Bradley J BackesDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Lung Biology Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Dustin J MalyDepartment of Chemistry, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address: djmaly@uw.edu.
Jeffrey A BluestoneDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: jeff.bluestone@ucsf.edu.
Feroz R PapaDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Lung Biology Center, University of California, San Francisco, San Francisco, CA 94143, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: frpapa@medicine.ucsf.edu.
QB3 · USUniversity of California, San Francisco · USUniversity of Washington · US

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2003 to 2019
$21.8M
MOLECULAR AND CELLULAR IMMUNOLOGYT32AI007334 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CYSTER, JASON G · 1988 to 2023
$11.0M
TRAINING IN MOLECULAR BIOPHYSICST32GM008268 · NIGMS · UNIVERSITY OF WASHINGTON · PI KOLLMAN, JUSTIN M, ZHENG, NING · 1988 to 2023
$8.6M
New Molecular Probes For Protein KinasesR01GM086858 · NIGMS · UNIVERSITY OF WASHINGTON · PI MALY, DUSTIN J · 2008 to 2025
$5.5M
Pharmacological Validation of IRE1 for Diabetes MellitusR01DK100623 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BACKES, BRADLEY J, MALY, DUSTIN J · 2014 to 2022
$4.6M
Cytoprotection of Beta Cells Through Modulation of Ire1Alpha FunctionR01DK080955 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PAPA, FEROZ R · 2009 to 2017
$3.0M
IMMUNOMODULATION OF TRANSPLANT REJECTION BY ANTI-CD3 MABR01AI046643 · NIAID · UNIVERSITY OF CHICAGO · PI BLUESTONE, JEFFREY A · 2000 to 2015
$1.8M
Attenuating ER and oxidative stress signaling to reduce cell degeneration in vivoR01DK095306 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI OAKES, SCOTT A., PAPA, FEROZ R · 2013 to 2016
$1.5M
NIAID NIH HHS R01 AI046643NIAID NIH HHS T32 AI007334NIDDK NIH HHS P30 DK063720NIDDK NIH HHS R01 DK080955NIDDK NIH HHS R01 DK095306NIDDK NIH HHS R01 DK100623NIGMS NIH HHS R01 GM086858NIGMS NIH HHS T32 GM008268
6 · The paper itself

Abstract

In cells experiencing unrelieved endoplasmic reticulum (ER) stress, the ER transmembrane kinase/endoribonuclease (RNase)-IRE1α-endonucleolytically degrades ER-localized mRNAs to promote apoptosis. Here we find that the ABL family of tyrosine kinases rheostatically enhances IRE1α's enzymatic activities, thereby potentiating ER stress-induced apoptosis. During ER stress, cytosolic ABL kinases localize to the ER membrane, where they bind, scaffold, and hyperactivate IRE1α's RNase. Imatinib-an anti-cancer tyrosine kinase inhibitor-antagonizes the ABL-IRE1α interaction, blunts IRE1α RNase hyperactivity, reduces pancreatic β cell apoptosis, and reverses type 1 diabetes (T1D) in the non-obese diabetic (NOD) mouse model. A mono-selective kinase inhibitor that allosterically attenuates IRE1α's RNase-KIRA8-also efficaciously reverses established diabetes in NOD mice by sparing β cells and preserving their physiological function. Our data support a model wherein ER-stressed β cells contribute to their own demise during T1D pathogenesis and implicate the ABL-IRE1α axis as a drug target for the treatment of an autoimmune disease.

Indexed as

Endoplasmic Reticulum StressSignal TransductionAnimalsApoptosisDiabetes Mellitus, Type 1EndoribonucleasesFemaleHumansImatinib MesylateInsulin-Secreting CellsMaleMice, Inbred NODModels, BiologicalProtein BindingProtein Serine-Threonine KinasesProto-Oncogene Proteins c-ablEndoribonucleasesERN1 protein, humanErn1 protein, mouseGNF-2 compoundImatinib MesylateProtein Serine-Threonine KinasesProto-Oncogene Proteins c-ablPyrimidinesapoptosisc-AblER stressimatinibinflammationinsulitisIRE1NODtype 1 diabetesunfolded protein responseβ cell dysfunction

Identifiers

PMID28380378
PMCPMC5497784
OpenAlexW4248517419

What OpenQuestion holds

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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.