{"id":7345,"date":"2018-03-02T00:00:00","date_gmt":"2018-03-01T22:00:00","guid":{"rendered":"https:\/\/irb.usi.ch\/uncategorized\/new-paper-by-the-molinari-lab\/"},"modified":"2020-07-15T15:36:16","modified_gmt":"2020-07-15T13:36:16","slug":"new-paper-by-the-molinari-lab","status":"publish","type":"post","link":"https:\/\/irb.usi.ch\/it\/news\/new-paper-by-the-molinari-lab\/","title":{"rendered":"New paper by the Molinari Lab"},"content":{"rendered":"<p class=\"news-publication\"><span>on<\/span> <span class=\"date-display-single\">March 2, 2018<\/span><\/p>\n<p class=\"rtejustify\">The endoplasmic reticulum (ER) is an intracellular organelle that produces all proteins destined to the cell surface, to the extracellular environments and to the organelles of the endocytic and secretory pathways. In a paper published on February 16th in the Journal of Biological Chemistry, Timothy Bergmann, Ilaria Fregno and Maurizio Molinari from the IRB, an institute affiliated to the Universit\u00e0 della Svizzera italiana, describe how human cells respond to ER stresses induced by chemical challenges or by the expression of disease-causing, mutant polypeptides. The study combines gene expression profiling and quantitative shotgun proteomics and has been performed in collaboration with Andrea Rinaldi and Francesco Bertoni (IOR) and Paola Picotti (ETH-Zurich).<\/p>\n<table align=\"left\" border=\"1\" cellpadding=\"1\" cellspacing=\"1\" >\n<tbody>\n<tr>\n<td><img alt=\"\" src=\"\/images\/new_paper_by_the_molinari_lab_feb2018.jpg\" ><\/td>\n<\/tr>\n<tr>\n<td class=\"rtejustify\">Gene expression profiling and quantitative shotgun proteomics (<strong>A<\/strong>) identified a restricted transcriptional (<strong>B<\/strong>) and translational response to misfolded proteins (BACE457, BACE457\u0394, CD3\u03b4 and CD3\u03b4<sub>QQQ <\/sub>as model polypeptides used in this study) in respect to chemically induced ER stresses (thapsigargin (TG) and tunicamycin (TM)). In response to misfolded, ER-retained proteins cells upregulate a limited set of UPR target genes that form a supramolecular complex (<strong>C<\/strong>) composed of ER chaperones, PDIs, ERAD and cell viability factors that prevent collapse of ER homeostasis and cell death.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p class=\"rtejustify\">The results show that chemically induced ER stress, as studied in the last decades, leads to the full activation of the so called \u201cUnfolded Protein Responses\u201d (UPR), which induce the transcription and translation of several hundred genes and eventually lead to multi compartmental failure and cell death. In contrast, expression of mutant, folding-defective polypeptides leads to the transcriptional and translational induction of a limited subset of UPR target genes, which are part of a supramolecular complex comprising ER chaperones, PDIs, ERAD and cell viability factors. In contrast to cellular responses to chemically induced ER stresses, responses to expression of misfolded proteins do not activate the PERK pathway of the UPR responsible for induction of apoptosis. This work shows that chemically-induced UPR, even if titrated down to induce similar ER stress levels as the expression of misfolded proteins, does not mimic cellular responses to latter. Transcriptional programs activated in response to perturbation of ER homeostasis by misfolded proteins are specific and tightly controlled, in fact only misfolded proteins that sequester a significant amount of BiP induce a UPR signature. All in all, these mechanisms prevent a premature collapse of ER homeostasis and activation of apoptotic programs.<\/p>\n<p class=\"rtejustify\">This work was supported by grants from Signora Alessandra, Alpha-ONE Foundation, Foundation for Research on Neurodegenerative Diseases, the Novartis Foundation, Comel and Gelu Foundations, Swiss National Science Foundation (SNF). Maurizio Molinari is supported by a Sinergia grant of the Swiss National Science Foundation.<\/p>\n<p class=\"rtejustify\"><strong>Article<\/strong><\/p>\n<p class=\"rtejustify\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29453283\" target=\"_blank\" rel=\"noopener noreferrer\">Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides<\/a><br \/>\nT. J. Bergmann, I. Fregno, F. Fumagalli, A. Rinaldi, F. Bertoni, P. J. Boersema, P. Picotti, M. Molinari<br \/>\nin J Biol Chem (2018)<\/p>\n","protected":false},"excerpt":{"rendered":"<p>on March 2, 2018 The endoplasmic reticulum (ER) is an intracellular organelle that produces all proteins destined to the cell surface, to the extracellular environments and to the organelles of the endocytic and secretory pathways. In a paper published on February 16th in the Journal of Biological Chemistry, Timothy Bergmann, Ilaria Fregno and Maurizio Molinari [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[16],"tags":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v15.7 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>New paper by the Molinari Lab - IRB USI<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/irb.usi.ch\/it\/news\/new-paper-by-the-molinari-lab\/\" \/>\n<meta property=\"og:locale\" content=\"it_IT\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"New paper by the Molinari Lab - IRB USI\" \/>\n<meta property=\"og:description\" content=\"on March 2, 2018 The endoplasmic reticulum (ER) is an intracellular organelle that produces all proteins destined to the cell surface, to the extracellular environments and to the organelles of the endocytic and secretory pathways. In a paper published on February 16th in the Journal of Biological Chemistry, Timothy Bergmann, Ilaria Fregno and Maurizio Molinari [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/irb.usi.ch\/it\/news\/new-paper-by-the-molinari-lab\/\" \/>\n<meta property=\"og:site_name\" content=\"IRB USI\" \/>\n<meta property=\"article:published_time\" content=\"2018-03-01T22:00:00+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2020-07-15T13:36:16+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/irb.usi.ch\/images\/new_paper_by_the_molinari_lab_feb2018.jpg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Tempo di lettura stimato\">\n\t<meta name=\"twitter:data1\" content=\"2 minuti\">\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebSite\",\"@id\":\"https:\/\/irb.usi.ch\/it\/#website\",\"url\":\"https:\/\/irb.usi.ch\/it\/\",\"name\":\"IRB USI\",\"description\":\"Institute for Research in Biomedicine\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":\"https:\/\/irb.usi.ch\/it\/?s={search_term_string}\",\"query-input\":\"required name=search_term_string\"}],\"inLanguage\":\"it-IT\"},{\"@type\":\"ImageObject\",\"@id\":\"https:\/\/irb.usi.ch\/it\/news\/new-paper-by-the-molinari-lab\/#primaryimage\",\"inLanguage\":\"it-IT\",\"url\":\"\/images\/new_paper_by_the_molinari_lab_feb2018.jpg\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/irb.usi.ch\/it\/news\/new-paper-by-the-molinari-lab\/#webpage\",\"url\":\"https:\/\/irb.usi.ch\/it\/news\/new-paper-by-the-molinari-lab\/\",\"name\":\"New paper by the Molinari Lab - IRB USI\",\"isPartOf\":{\"@id\":\"https:\/\/irb.usi.ch\/it\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\/\/irb.usi.ch\/it\/news\/new-paper-by-the-molinari-lab\/#primaryimage\"},\"datePublished\":\"2018-03-01T22:00:00+00:00\",\"dateModified\":\"2020-07-15T13:36:16+00:00\",\"author\":{\"@id\":\"https:\/\/irb.usi.ch\/it\/#\/schema\/person\/c9b66c69925e1b0c558072acbadf4156\"},\"breadcrumb\":{\"@id\":\"https:\/\/irb.usi.ch\/it\/news\/new-paper-by-the-molinari-lab\/#breadcrumb\"},\"inLanguage\":\"it-IT\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/irb.usi.ch\/it\/news\/new-paper-by-the-molinari-lab\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/irb.usi.ch\/it\/news\/new-paper-by-the-molinari-lab\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"item\":{\"@type\":\"WebPage\",\"@id\":\"https:\/\/irb.usi.ch\/it\/\",\"url\":\"https:\/\/irb.usi.ch\/it\/\",\"name\":\"Home\"}},{\"@type\":\"ListItem\",\"position\":2,\"item\":{\"@type\":\"WebPage\",\"@id\":\"https:\/\/irb.usi.ch\/.\/news\/\",\"url\":\"https:\/\/irb.usi.ch\/.\/news\/\",\"name\":\"News\"}},{\"@type\":\"ListItem\",\"position\":3,\"item\":{\"@type\":\"WebPage\",\"@id\":\"https:\/\/irb.usi.ch\/it\/news\/new-paper-by-the-molinari-lab\/\",\"url\":\"https:\/\/irb.usi.ch\/it\/news\/new-paper-by-the-molinari-lab\/\",\"name\":\"New paper by the Molinari Lab\"}}]},{\"@type\":\"Person\",\"@id\":\"https:\/\/irb.usi.ch\/it\/#\/schema\/person\/c9b66c69925e1b0c558072acbadf4156\",\"name\":\"AD_Dave\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","_links":{"self":[{"href":"https:\/\/irb.usi.ch\/it\/wp-json\/wp\/v2\/posts\/7345"}],"collection":[{"href":"https:\/\/irb.usi.ch\/it\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/irb.usi.ch\/it\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/irb.usi.ch\/it\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/irb.usi.ch\/it\/wp-json\/wp\/v2\/comments?post=7345"}],"version-history":[{"count":0,"href":"https:\/\/irb.usi.ch\/it\/wp-json\/wp\/v2\/posts\/7345\/revisions"}],"wp:attachment":[{"href":"https:\/\/irb.usi.ch\/it\/wp-json\/wp\/v2\/media?parent=7345"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/irb.usi.ch\/it\/wp-json\/wp\/v2\/categories?post=7345"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/irb.usi.ch\/it\/wp-json\/wp\/v2\/tags?post=7345"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}