Li, JuyingYin, Helen L.Yuan, Junying2019-10-052008Li, Juying, Helen L. Yin, and Junying Yuan. 2008. “Flightless-I Regulates Proinflammatory Caspases by Selectively Modulating Intracellular Localization and Caspase Activity.” The Journal of Cell Biology 181 (2): 321–33. https://doi.org/10.1083/jcb.200711082.0021-95251540-8140http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483524Caspase-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-1 beta (IL-1 beta) 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-1 beta maturation. Our results suggest that Flightless-I may be a bona. de caspase-1 inhibitor that acts through a mechanism similar to that of cytokine response modi. er A, a potent caspase-1 inhibitor from the cowpox virus. Our study provides a new mechanism controlling the localization and activation of proinflammatory caspases.en-USJournal Article2019-10-0510.1083/jcb.200711082