title: Shigella-induced apoptosis is dependent on caspase-1 which binds to IpaB.
abstract: We report here that the Shigella invasion plasmid antigen (Ipa)B, which is sufficient to induce apoptosis in macrophages, binds to caspase (Casp)-1, but not to Casp-2 or Casp-3. Casp-1 is activated and its specific substrate interleukin-1beta is cleaved shortly after Shigella infection. Macrophages isolated from Casp-1 knock-out mice are not susceptible to Shigella-induced apoptosis, although they respond normally to other apoptotic stimuli. Shigella kills macrophages from casp-3, casp-11, and p53 knock-out mice as well as macrophages overexpressing Bcl-2. We propose that Shigella induces apoptosis by directly activating Casp-1 through IpaB, bypassing signal transduction events and caspases upstream of Casp-1. Taken together these data indicate that Shigella-induced apoptosis is distinct from other forms of apoptosis and seems uniquely dependent on Casp-1.
authors.affiliation: Skirball Institute, Department of Microbiology and Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hilbi
authors.forename: J E
authors.initials: JE
authors.lastname: Moss
authors.forename: D
authors.initials: D
authors.lastname: Hersh
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Arondel
authors.forename: S
authors.initials: S
authors.lastname: Banerjee
authors.forename: R A
authors.initials: RA
authors.lastname: Flavell
authors.forename: J
authors.initials: J
authors.lastname: Yuan
authors.forename: P J
authors.initials: PJ
authors.lastname: Sansonetti
authors.forename: A
authors.initials: A
authors.lastname: Zychlinsky
mesh_terms: D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D012760:Shigella / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C087447:ipaB protein, Shigella; D020170:Caspase 1