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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...

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Detalles Bibliográficos
Autores principales: Li, Juying, Yin, Helen L., Yuan, Junying
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
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.
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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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