Assembly and regulation of ASC specks
The inflammasome adapter ASC links activated inflammasome sensors to the effector molecule pro-caspase-1. Recruitment of pro-caspase-1 to ASC promotes the autocatalytic activation of caspase-1, which leads to the release of pro-inflammatory cytokines, such as IL-1β. Upon triggering of inflammasome s...
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creator | Hoss, Florian Rodriguez-Alcazar, Juan F. Latz, Eicke |
description | The inflammasome adapter ASC links activated inflammasome sensors to the effector molecule pro-caspase-1. Recruitment of pro-caspase-1 to ASC promotes the autocatalytic activation of caspase-1, which leads to the release of pro-inflammatory cytokines, such as IL-1β. Upon triggering of inflammasome sensors, ASC assembles into large helical fibrils that interact with each other serving as a supramolecular signaling platform termed the ASC speck. Alternative splicing, post-translational modifications of ASC, as well as interaction with other proteins can perturb ASC function. In several inflammatory diseases, ASC specks can be found in the extracellular space and its presence correlates with poor prognosis. Here, we review the role of ASC in inflammation, and focus on the structural mechanisms that lead to ASC speck formation, the regulation of ASC function during inflammasome assembly, and the importance of ASC specks in disease. |
doi_str_mv | 10.1007/s00018-016-2396-6 |
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Recruitment of pro-caspase-1 to ASC promotes the autocatalytic activation of caspase-1, which leads to the release of pro-inflammatory cytokines, such as IL-1β. Upon triggering of inflammasome sensors, ASC assembles into large helical fibrils that interact with each other serving as a supramolecular signaling platform termed the ASC speck. Alternative splicing, post-translational modifications of ASC, as well as interaction with other proteins can perturb ASC function. In several inflammatory diseases, ASC specks can be found in the extracellular space and its presence correlates with poor prognosis. Here, we review the role of ASC in inflammation, and focus on the structural mechanisms that lead to ASC speck formation, the regulation of ASC function during inflammasome assembly, and the importance of ASC specks in disease.</description><identifier>ISSN: 1420-682X</identifier><identifier>EISSN: 1420-9071</identifier><identifier>DOI: 10.1007/s00018-016-2396-6</identifier><identifier>PMID: 27761594</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adapter proteins ; Alternative splicing ; Antigens ; Apoptosis ; Apoptosis Regulatory Proteins - chemistry ; Apoptosis Regulatory Proteins - genetics ; Apoptosis Regulatory Proteins - metabolism ; Assembly ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Carrier Proteins - metabolism ; Caspase-1 ; Cell Biology ; Cytokines ; Enzymes ; Extracellular Matrix - metabolism ; Fibrils ; Gene expression ; Humans ; IL-1β ; Immune system ; Inflammasomes ; Inflammasomes - metabolism ; Inflammation ; Inflammation - metabolism ; Inflammation - pathology ; Inflammatory diseases ; Kinases ; Life Sciences ; Medical research ; Melanoma ; Pathogens ; Post-translation ; Protein Isoforms - chemistry ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Protein Multimerization ; Protein Processing, Post-Translational ; Review ; RNA Splicing ; Sensors ; Signal transduction ; Splicing ; Tumor necrosis factor-TNF</subject><ispartof>Cellular and molecular life sciences : CMLS, 2017-04, Vol.74 (7), p.1211-1229</ispartof><rights>Springer International Publishing 2016</rights><rights>Springer International Publishing 2016.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-55becfad7d0e61f69fed45a44ed0103fd5971ec7dadce0855cf707ca180e3ffb3</citedby><cites>FETCH-LOGICAL-c532t-55becfad7d0e61f69fed45a44ed0103fd5971ec7dadce0855cf707ca180e3ffb3</cites><orcidid>0000-0003-1488-5666</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11107573/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11107573/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27915,27916,41479,42548,51310,53782,53784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27761594$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hoss, Florian</creatorcontrib><creatorcontrib>Rodriguez-Alcazar, Juan F.</creatorcontrib><creatorcontrib>Latz, Eicke</creatorcontrib><title>Assembly and regulation of ASC specks</title><title>Cellular and molecular life sciences : CMLS</title><addtitle>Cell. Mol. Life Sci</addtitle><addtitle>Cell Mol Life Sci</addtitle><description>The inflammasome adapter ASC links activated inflammasome sensors to the effector molecule pro-caspase-1. Recruitment of pro-caspase-1 to ASC promotes the autocatalytic activation of caspase-1, which leads to the release of pro-inflammatory cytokines, such as IL-1β. Upon triggering of inflammasome sensors, ASC assembles into large helical fibrils that interact with each other serving as a supramolecular signaling platform termed the ASC speck. Alternative splicing, post-translational modifications of ASC, as well as interaction with other proteins can perturb ASC function. In several inflammatory diseases, ASC specks can be found in the extracellular space and its presence correlates with poor prognosis. Here, we review the role of ASC in inflammation, and focus on the structural mechanisms that lead to ASC speck formation, the regulation of ASC function during inflammasome assembly, and the importance of ASC specks in disease.</description><subject>Adapter proteins</subject><subject>Alternative splicing</subject><subject>Antigens</subject><subject>Apoptosis</subject><subject>Apoptosis Regulatory Proteins - chemistry</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Assembly</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Carrier Proteins - metabolism</subject><subject>Caspase-1</subject><subject>Cell Biology</subject><subject>Cytokines</subject><subject>Enzymes</subject><subject>Extracellular Matrix - metabolism</subject><subject>Fibrils</subject><subject>Gene expression</subject><subject>Humans</subject><subject>IL-1β</subject><subject>Immune system</subject><subject>Inflammasomes</subject><subject>Inflammasomes - metabolism</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Inflammatory diseases</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>Medical research</subject><subject>Melanoma</subject><subject>Pathogens</subject><subject>Post-translation</subject><subject>Protein Isoforms - chemistry</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Protein Multimerization</subject><subject>Protein Processing, Post-Translational</subject><subject>Review</subject><subject>RNA Splicing</subject><subject>Sensors</subject><subject>Signal transduction</subject><subject>Splicing</subject><subject>Tumor necrosis factor-TNF</subject><issn>1420-682X</issn><issn>1420-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkV1LHDEUhkNR6kf7A3pTBkTwZuo5mcnXlSxLq4LghS30LmQzJ-vY2Zk12RH8982yq2ih4lUC5zlvyPsw9gXhGwKo0wQAqEtAWfLKyFJ-YPtYcygNKNzZ3qXmv_fYQUp3GRaay49sjyslUZh6nx1PUqLFrHssXN8UkeZj51bt0BdDKCY30yItyf9Jn9hucF2iz9vzkP368f3n9KK8uj6_nE6uSi8qviqFmJEPrlENkMQgTaCmFq6uqQGEKjTCKCSvGtd4Ai2EDwqUd6iBqhBm1SE72-Qux9mCMtSvouvsMrYLFx_t4Fr7etK3t3Y-PFhEBCVUlRNOtglxuB8preyiTZ66zvU0jMmi1qhqYzS8A62EAMO5yOjRP-jdMMY-V2G5NEKilFy9RaHOhVfaGMwUbigfh5QihefvIdi1VrvRarNWu9ZqZd75-rKX540njxngGyDlUT-n-OLp_6b-BT5Aq5c</recordid><startdate>20170401</startdate><enddate>20170401</enddate><creator>Hoss, Florian</creator><creator>Rodriguez-Alcazar, Juan F.</creator><creator>Latz, Eicke</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1488-5666</orcidid></search><sort><creationdate>20170401</creationdate><title>Assembly and regulation of ASC specks</title><author>Hoss, Florian ; Rodriguez-Alcazar, Juan F. ; Latz, Eicke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-55becfad7d0e61f69fed45a44ed0103fd5971ec7dadce0855cf707ca180e3ffb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adapter proteins</topic><topic>Alternative splicing</topic><topic>Antigens</topic><topic>Apoptosis</topic><topic>Apoptosis Regulatory Proteins - chemistry</topic><topic>Apoptosis Regulatory Proteins - genetics</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Assembly</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Carrier Proteins - metabolism</topic><topic>Caspase-1</topic><topic>Cell Biology</topic><topic>Cytokines</topic><topic>Enzymes</topic><topic>Extracellular Matrix - metabolism</topic><topic>Fibrils</topic><topic>Gene expression</topic><topic>Humans</topic><topic>IL-1β</topic><topic>Immune system</topic><topic>Inflammasomes</topic><topic>Inflammasomes - metabolism</topic><topic>Inflammation</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Inflammatory diseases</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Medical research</topic><topic>Melanoma</topic><topic>Pathogens</topic><topic>Post-translation</topic><topic>Protein Isoforms - chemistry</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Protein Multimerization</topic><topic>Protein Processing, Post-Translational</topic><topic>Review</topic><topic>RNA Splicing</topic><topic>Sensors</topic><topic>Signal transduction</topic><topic>Splicing</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hoss, Florian</creatorcontrib><creatorcontrib>Rodriguez-Alcazar, Juan F.</creatorcontrib><creatorcontrib>Latz, Eicke</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cellular and molecular life sciences : CMLS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hoss, Florian</au><au>Rodriguez-Alcazar, Juan F.</au><au>Latz, Eicke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assembly and regulation of ASC specks</atitle><jtitle>Cellular and molecular life sciences : CMLS</jtitle><stitle>Cell. Mol. Life Sci</stitle><addtitle>Cell Mol Life Sci</addtitle><date>2017-04-01</date><risdate>2017</risdate><volume>74</volume><issue>7</issue><spage>1211</spage><epage>1229</epage><pages>1211-1229</pages><issn>1420-682X</issn><eissn>1420-9071</eissn><abstract>The inflammasome adapter ASC links activated inflammasome sensors to the effector molecule pro-caspase-1. Recruitment of pro-caspase-1 to ASC promotes the autocatalytic activation of caspase-1, which leads to the release of pro-inflammatory cytokines, such as IL-1β. Upon triggering of inflammasome sensors, ASC assembles into large helical fibrils that interact with each other serving as a supramolecular signaling platform termed the ASC speck. Alternative splicing, post-translational modifications of ASC, as well as interaction with other proteins can perturb ASC function. In several inflammatory diseases, ASC specks can be found in the extracellular space and its presence correlates with poor prognosis. Here, we review the role of ASC in inflammation, and focus on the structural mechanisms that lead to ASC speck formation, the regulation of ASC function during inflammasome assembly, and the importance of ASC specks in disease.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>27761594</pmid><doi>10.1007/s00018-016-2396-6</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0003-1488-5666</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adapter proteins Alternative splicing Antigens Apoptosis Apoptosis Regulatory Proteins - chemistry Apoptosis Regulatory Proteins - genetics Apoptosis Regulatory Proteins - metabolism Assembly Biochemistry Biomedical and Life Sciences Biomedicine Cancer Carrier Proteins - metabolism Caspase-1 Cell Biology Cytokines Enzymes Extracellular Matrix - metabolism Fibrils Gene expression Humans IL-1β Immune system Inflammasomes Inflammasomes - metabolism Inflammation Inflammation - metabolism Inflammation - pathology Inflammatory diseases Kinases Life Sciences Medical research Melanoma Pathogens Post-translation Protein Isoforms - chemistry Protein Isoforms - genetics Protein Isoforms - metabolism Protein Multimerization Protein Processing, Post-Translational Review RNA Splicing Sensors Signal transduction Splicing Tumor necrosis factor-TNF |
title | Assembly and regulation of ASC specks |
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