Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity

• DOI: 10.1084/jem.20172222
• Publication Date: 2018-02-06T14:45:19Z
• Authors: Dave Boucher; Mercedes Monteleone; Rebecca C. Coll; Kaiwen W. Chen; Connie M. Ross; Jessica L. Teo; Guillermo A. Gomez; Caroline L. Holley; Damien Bierschenk; Katryn J. Stacey; Alpha S. Yap; Jelena S. Bezbradica; Kate Schroder
• Keywords: Tetramer; AIM2; Caspase 8; Cleavage (geology)

Host-protective caspase-1 activity must be tightly regulated to prevent pathology, but mechanisms controlling the duration of cellular are unknown. Caspase-1 is activated on inflammasomes, signaling platforms that facilitate dimerization and autoprocessing. Previous studies with recombinant protein identified a tetramer composed two p20 p10 subunits (p20/p10) as an active species. In this study, we report in cell, dominant species dimers elicited by inflammasomes fact full-length p46 transient species, p33/p10. Further p33/p10 autoprocessing occurs kinetics specified inflammasome size cell type, releases p20/p10 from inflammasome, whereupon becomes unstable cells protease terminated. The inflammasome–caspase-1 complex thus functions holoenzyme directs location also incorporates intrinsic self-limiting mechanism ensures timely deactivation. This signal shutdown offers molecular basis for nature, coordinated timing, inflammasome-dependent inflammatory responses.