Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity

Juying Li, Helen L. Yin, Junying Yuan

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)321-333
Number of pages13
JournalJournal of Cell Biology
Volume181
Issue number2
DOIs
StatePublished - Apr 21 2008

ASJC Scopus subject areas

  • Cell Biology

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