Plaguing Caspase-1 Through Rac

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Science  25 Jun 2004:
Vol. 304, Issue 5679, pp. 1879
DOI: 10.1126/science.304.5679.1879b

The Yersinia bacteria, whose most notorious member (Y. pestis) is the causative agent of bubonic plague, inject Yop proteins into target cells. These proteins prevent phagocytosis and suppress the inflammatory response. For instance, YopP interferes with NF-κB activation and the transcription of proinflammatory cytokines, whereas the guanosine triphosphatase (GTPase)-activating protein YopE inhibits Rho-family GTPases, and thereby blocks cytoskeletal rearrangements involved in phagocytosis. Noticing that Mf4/4 murine macrophages infected with YopP-deficient Y. enterocolitica secreted more interleukin-6 (IL-6) than did macrophages infected with wild-type bacteria, but not more IL-1β, Schotte et al. discovered that the former contained increased cytoplasmic concentrations of proIL-1β and that YopE inhibited proIL-1β processing. ProIL-1β is converted into IL-1β by caspase-1, and in cells transfected with procaspase-1 and proIL-1β, YopE inhibited autocatalytic processing of procaspase-1 and hence processing of proIL-1β. Cells expressing constitutively active Rac1 (a Rho family GTPase) showed increased procaspase-1 autoproteolysis and secretion of IL-1β, whereas dominant-negative Rac1 or pharmacological inhibition of Rho family GTPase activity suppressed both. These data uncover an unexpected role for Rac1 in caspase-1 activation. — EMA

J. Biol. Chem. 279, 25134 (2004).

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