{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:31:37Z","timestamp":1790508697381,"version":"4.1.0"},"reference-count":38,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6448","funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2019,7,5]]},"abstract":"<jats:title>Linking protein misfolding and innate immunity<\/jats:title>\n                  <jats:p>\n                    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\n                    <jats:italic>et al.<\/jats:italic>\n                    identified a pathway, dependent on heme-regulated inhibitor, eukaryotic initiation factor 2\u03b1, 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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Science<\/jats:italic>\n                    , this issue p.\n                    <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" related-article-type=\"in-this-issue\" xlink:href=\"10.1126\/science.aaw4144\">eaaw4144<\/jats:related-article>\n                    ; see also p.\n                    <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" issue=\"6448\" page=\"28\" related-article-type=\"in-this-issue\" vol=\"365\" xlink:href=\"10.1126\/science.aay0987\">28<\/jats:related-article>\n                  <\/jats:p>","DOI":"10.1126\/science.aaw4144","type":"journal-article","created":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T19:05:56Z","timestamp":1562267156000},"source":"Crossref","is-referenced-by-count":125,"title":["The heme-regulated inhibitor is a cytosolic sensor of protein misfolding that controls innate immune signaling"],"prefix":"10.1126","volume":"365","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2492-0736","authenticated-orcid":true,"given":"Mena","family":"Abdel-Nour","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5870-8288","authenticated-orcid":true,"given":"Leticia A. 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