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Journal articles
Interactome Screening Identifies the ER Luminal Chaperone Hsp47 as a Regulator of the Unfolded Protein Response Transducer IRE1 alpha
Denisse Sepulveda
Diego Rojas-Rivera
Diego A. Rodriguez
Jody Groenendyk
1
Andres Kohler
Cynthia Lebeaupin
2
Shinya Ito
Hery Urra
Amado Carreras-Sureda
Younis Hazari
Mireille Vasseur-Cognet
3
Maruf M. U. Ali
4
Eric Chevet
5, 6
Gisela Campos
Patricio Godoy
Tomas Vaisar
Beatrice Bailly-Maitre
2
Kazuhiro Nagata
Marek Michalak
1
Jimena Sierralta
Claudio Hetz
*
Denisse Sepulveda
Author
Diego Rojas-Rivera
Author
Diego A. Rodriguez
Author
Jody Groenendyk 1
Author
Amado Carreras-Sureda
Author
Younis Hazari
Author
Mireille Vasseur-Cognet 3
Author
Maruf M. U. Ali 4
Author
Beatrice Bailly-Maitre 2
Author
Kazuhiro Nagata
Author
Marek Michalak 1
Author
Jimena Sierralta
Author
Claudio Hetz
Correspondent author
1
University of Alberta (116 St & 85 Ave, Edmonton, AB T6G 2R3 - Canada)
2
C3M - Centre méditerranéen de médecine moléculaire (Hôpital de l'Archet, 151 rte Saint Antoine de Ginestiere 06204 Nice Cedex 3 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1065 (101, rue de Tolbiac, 75013 Paris - France)
- UCA - Université Côte d'Azur (Parc Valrose, 28 avenue Valrose 06108 Nice Cedex 2 - France)
- UNS - Université Nice Sophia Antipolis (... - 2019) (Parc Valrose - BP 2135 - 06103 Nice cedex 2 - France)
- COMUE UCA - COMUE Université Côte d'Azur (2015 - 2019) (Parc Valrose, 28 avenue Valrose 06108 Nice Cedex 2 - France)
3
IEES - Institut d'écologie et des sciences de l'environnement de Paris (UPMC, campus de Jussieu - Bât A - Paris (75005)
UPMC, campus de Jussieu - Tour 56/66 - Paris (75005)
AgroParisTech-INRA - Grignon (78)
INRA - Versailles (78)
IRD - Bondy (93)
U-PEC - Créteil (94)
- France)
- INRA - Institut National de la Recherche Agronomique : UMRA1392 (France)
- UPMC - Université Pierre et Marie Curie - Paris 6 : UM113 (4 place Jussieu - 75005 Paris - France)
- UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12 (61 avenue du Général de Gaulle - 94010 Créteil cedex - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7618 (France)
4
Imperial College London (South Kensington Campus, London SW7 2AZ - United Kingdom)
5
COSS - Chemistry, Oncogenesis, Stress and Signaling (Université de Rennes1 - CLCC Eugène Marquis, Rue de la Bataille Flandres Dunkerque, Bat D, 35042 Rennes - France)
- UR1 - Université de Rennes 1 (2 rue du Thabor - CS 46510 - 35065 Rennes cedex - France)
- UNIV-RENNES - Université de Rennes (France)
- CRLCC - CRLCC Eugène Marquis (Avenue Bataille Flandres-Dunkerque 35042 RENNES CEDEX - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1242 (101, rue de Tolbiac, 75013 Paris - France)
6
CRLCC - CRLCC Eugène Marquis (Avenue Bataille Flandres-Dunkerque 35042 RENNES CEDEX - France)
Abstract : Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR). IRE1α is a major UPR transducer, determining cell fate under ER stress. We used an interactome screening to unveil several regulators of the UPR, highlighting the ER chaperone Hsp47 as the major hit. Cellular and biochemical analysis indicated that Hsp47 instigates IRE1α signaling through a physical interaction. Hsp47 directly binds to the ER luminal domain of IRE1α with high affinity, displacing the negative regulator BiP from the complex to facilitate IRE1α oligomerization. The regulation of IRE1α signaling by Hsp47 is evolutionarily conserved as validated using fly and mouse models of ER stress. Hsp47 deficiency sensitized cells and animals to experimental ER stress, revealing the significance of Hsp47 to global proteostasis maintenance. We conclude that Hsp47 adjusts IRE1α signaling by fine-tuning the threshold to engage an adaptive UPR.
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Journal articles
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01710048
Contributor : Laurent Jonchère <>
Submitted on : Thursday, February 15, 2018 - 3:25:01 PM
Last modification on : Wednesday, February 24, 2021 - 10:55:47 AM
Contributor : Laurent Jonchère <>
Submitted on : Thursday, February 15, 2018 - 3:25:01 PM
Last modification on : Wednesday, February 24, 2021 - 10:55:47 AM
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Identifiers
- HAL Id : hal-01710048, version 1
- DOI : 10.1016/j.molcel.2017.12.028
- PUBMED : 29351844
Collections
UNIV-RENNES1 | OSS | CNRS | INRA | MARQUIS | UPEC-UPEM | FNCLCC | BIOSIT | UR1-UFR-SVE | UNICE | UNIV-RENNES | UNIV-COTEDAZUR | SORBONNE-UNIVERSITE | IEES | SU-SCIENCES | UPEC | INRAE | UP-SCIENCES | SU-TI
Citation
Denisse Sepulveda, Diego Rojas-Rivera, Diego A. Rodriguez, Jody Groenendyk, Andres Kohler, et al.. Interactome Screening Identifies the ER Luminal Chaperone Hsp47 as a Regulator of the Unfolded Protein Response Transducer IRE1 alpha. Molecular Cell, Elsevier, 2018, 69 (2), pp.238-252.e7. ⟨10.1016/j.molcel.2017.12.028⟩. ⟨hal-01710048⟩
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