Caspase-1 interdomain linker cleavage is required for pyroptosis Journal Article
| Authors: | Ball, D. P.; Taabazuing, C. Y.; Griswold, A. R.; Orth, E. L.; Rao, S. D.; Kotliar, I. B.; Vostal, L. E.; Johnson, D. C.; Bachovchin, D. A. |
| Article Title: | Caspase-1 interdomain linker cleavage is required for pyroptosis |
| Abstract: | Pathogen-related signals induce a number of cytosolic pattern-recognition receptors (PRRs) to form canonical inflammasomes, which activate pro-caspase-1 and trigger pyroptotic cell death. All well-studied inflammasome-forming PRRs oligomerize with the adapter protein ASC (apoptosis-associated speck-like protein containing a CARD) to generate a large structure in the cytosol, which induces the dimerization, autoproteolysis, and activation of the pro-caspase-1 zymogen. However, several PRRs can also directly interact with pro-caspase-1 without ASC, forming smaller "ASC-independent" inflammasomes. It is currently thought that little, if any, pro-caspase-1 autoproteolysis occurs during, and is not required for, ASC-independent inflammasome signaling. Here, we show that the related human PRRs NLRP1 and CARD8 exclusively form ASC-dependent and ASC-independent inflammasomes, respectively, identifying CARD8 as the first canonical inflammasome-forming PRR that does not form an ASC-containing signaling platform. Despite their different structures, we discovered that both the NLRP1 and CARD8 inflammasomes require pro-caspase-1 autoproteolysis between the small and large catalytic subunits to induce pyroptosis. Thus, pro-caspase-1 self-cleavage is a required regulatory step for pyroptosis induced by human canonical inflammasomes. © 2020 Ball et al. |
| Journal Title: | Life Science Alliance |
| Volume: | 3 |
| Issue: | 3 |
| ISSN: | 2575-1077 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2020-03-01 |
| Start Page: | e202000664 |
| Language: | English |
| DOI: | 10.26508/lsa.202000664 |
| PUBMED: | 32051255 |
| PROVIDER: | scopus |
| PMCID: | PMC7025033 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 March 2020 -- Source: Scopus |
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