title: Assembly and regulation of ASC specks.
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.
authors.affiliation: Institute of Innate Immunity, University Hospitals, University of Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Hoss
authors.affiliation: Institute of Innate Immunity, University Hospitals, University of Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Rodriguez-Alcazar
authors.affiliation: Institute of Innate Immunity, University Hospitals, University of Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany. eicke.latz@uni-bonn.de.|Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA. eicke.latz@uni-bonn.de.|German Center for Neurodegenerative Diseases, Bonn, Germany. eicke.latz@uni-bonn.de.|Department of Cancer Research and Molecular Medicine, Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway. eicke.latz@uni-bonn.de.
authors.forename: Eicke
authors.identifier: 0000-0003-1488-5666
authors.initials: E
authors.lastname: Latz
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D012326:RNA Splicing
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D058847:Inflammasomes; C436144:LLID-114769 protein, human; D020033:Protein Isoforms
keywords: CARD; COP; Fibril; POP; PTM; PYD; Prionoid; Speck