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Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity
Caspase-1 and caspase-11 are proinflammatory caspases that regulate cytokine production and leukocyte migration during pathogen infection. In an attempt to identify new intracellular regulators of caspase-11, we found that Flightless-I, a member of the gelsolin superfamily of actin-remodeling protei...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2315678/ https://www.ncbi.nlm.nih.gov/pubmed/18411310 http://dx.doi.org/10.1083/jcb.200711082 |
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author | Li, Juying Yin, Helen L. Yuan, Junying |
author_facet | Li, Juying Yin, Helen L. Yuan, Junying |
author_sort | Li, Juying |
collection | PubMed |
description | Caspase-1 and caspase-11 are proinflammatory caspases that regulate cytokine production and leukocyte migration during pathogen infection. In an attempt to identify new intracellular regulators of caspase-11, we found that Flightless-I, a member of the gelsolin superfamily of actin-remodeling proteins, interacts and regulates both caspase-11 and caspase-1. Flightless-I targets caspase-11 to the Triton X-100–insoluble cytoskeleton fraction and the cell leading edge. In addition, Flightless-I inhibits caspase-1 activation and caspase-1–mediated interleukine-1β (IL-1β) maturation. The physiological relevance of these findings is supported by the opposing effects of Flightless-I overexpression and knockdown on caspase-1 activity and IL-1β maturation. Our results suggest that Flightless-I may be a bona fide caspase-1 inhibitor that acts through a mechanism similar to that of cytokine response modifier A, a potent caspase-1 inhibitor from the cowpox virus. Our study provides a new mechanism controlling the localization and activation of proinflammatory caspases. |
format | Text |
id | pubmed-2315678 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-23156782008-10-21 Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity Li, Juying Yin, Helen L. Yuan, Junying J Cell Biol Research Articles Caspase-1 and caspase-11 are proinflammatory caspases that regulate cytokine production and leukocyte migration during pathogen infection. In an attempt to identify new intracellular regulators of caspase-11, we found that Flightless-I, a member of the gelsolin superfamily of actin-remodeling proteins, interacts and regulates both caspase-11 and caspase-1. Flightless-I targets caspase-11 to the Triton X-100–insoluble cytoskeleton fraction and the cell leading edge. In addition, Flightless-I inhibits caspase-1 activation and caspase-1–mediated interleukine-1β (IL-1β) maturation. The physiological relevance of these findings is supported by the opposing effects of Flightless-I overexpression and knockdown on caspase-1 activity and IL-1β maturation. Our results suggest that Flightless-I may be a bona fide caspase-1 inhibitor that acts through a mechanism similar to that of cytokine response modifier A, a potent caspase-1 inhibitor from the cowpox virus. Our study provides a new mechanism controlling the localization and activation of proinflammatory caspases. The Rockefeller University Press 2008-04-21 /pmc/articles/PMC2315678/ /pubmed/18411310 http://dx.doi.org/10.1083/jcb.200711082 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Li, Juying Yin, Helen L. Yuan, Junying Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity |
title | Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity |
title_full | Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity |
title_fullStr | Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity |
title_full_unstemmed | Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity |
title_short | Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity |
title_sort | flightless-i regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2315678/ https://www.ncbi.nlm.nih.gov/pubmed/18411310 http://dx.doi.org/10.1083/jcb.200711082 |
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