The heme-regulated inhibitor is a cytosolic sensor of protein misfolding that controls innate immune signaling-Reference-Cited by-同舟云学术

The heme-regulated inhibitor is a cytosolic sensor of protein misfolding that controls innate immune signaling

Published:2019-07-05 Issue:6448 Volume:365 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Abdel-Nour Mena¹^ORCID,Carneiro Leticia A. M.¹^ORCID,Downey Jeffrey²,Tsalikis Jessica¹,Outlioua Ahmed³⁴^ORCID,Prescott Dave¹⁵^ORCID,Da Costa Leandro Silva³^ORCID,Hovingh Elise S.¹,Farahvash Armin¹^ORCID,Gaudet Ryan G.⁶,Molinaro Raphael¹,van Dalen Rob¹^ORCID,Lau Charles C. Y.¹⁵^ORCID,Azimi Farshad C.¹^ORCID,Escalante Nichole K.⁵^ORCID,Trotman-Grant Aaron⁵^ORCID,Lee Jeffrey E.¹,Gray-Owen Scott D.⁶^ORCID,Divangahi Maziar²^ORCID,Chen Jane-Jane⁷,Philpott Dana J.⁵,Arnoult Damien³^ORCID,Girardin Stephen E.¹^ORCID

Affiliation:

1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

2. Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.

3. INSERM U1197, Hôpital Paul Brousse, Bâtiment Lavoisier, 94807 Villejuif Cedex, France.

4. Molecular Genetics and Immunophysiopathology Research Team, Health and Environment Laboratory, Aïn Chock Faculty of Sciences, Hassan II University of Casablanca, Casablanca, Morocco.

5. Department of Immunology, University of Toronto, Toronto, ON, Canada.

6. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

7. Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.

Abstract

Linking protein misfolding and innate immunity Multiple innate immune sensors undergo rapid assembly into large complexes known as signalosomes. This is an essential step during cellular responses to microbes and danger signals. How this process is regulated to avoid accumulation of potentially toxic protein aggregates remains poorly understood. Abdel-Nour et al. identified a pathway, dependent on heme-regulated inhibitor, eukaryotic initiation factor 2α, activating transcription factor 4, and heat shock protein B8, which controls the folding and scaffolding of innate immune sensors, allowing optimal proinflammatory signaling (see the Perspective by Pierre). The pathway appears to mirror the endoplasmic reticulum unfolded protein response (UPR), and so was named the cytosolic UPR (cUPR). The cUPR may represent a general mechanism to control protein misfolding in cells. Science , this issue p. eaaw4144 ; see also p. 28

Funder

Canadian Institutes of Health Research

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference38 articles.

1. Phosphorylation of initiation factor 2α by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast

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4. Regulation of protein synthesis in rabbit reticulocyte lysates: The heme-regulated protein kinase (HRI) and double stranded RNA induced protein kinase (dRI) phosphorylate the same site(s) on initiation factor eIF-2

5. Phosphorylation of eIF2α in response to 26S proteasome inhibition is mediated by the haem-regulated inhibitor (HRI) kinase

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