Shigella-induced Apoptosis Is Dependent on Caspase-1 Which Binds to IpaB*

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-1β 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, andp53 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.

• Publication year

  1998

• Venue

  Journal of Biological Chemistry

• Publication date

  1998-12-04

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.273.49.32895PMID 9830039
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Shigella appears to induce apoptosis by directly activating caspase-1 through IpaB, bypassing upstream signal transduction events and caspases.

  Confidence 0.93

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• Macrophages lacking caspase-1 are not susceptible to Shigella-induced apoptosis, whereas macrophages from caspase-3, caspase-11, or p53 knock-out mice and Bcl-2-overexpressing macrophages remain susceptible.

  Confidence 0.94

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• Caspase-1 is activated and interleukin-1β is cleaved shortly after Shigella infection.

  Confidence 0.97

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• IpaB binds caspase-1 but not caspase-2 or caspase-3.

  Confidence 0.98

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review

• bcl-2

  anti-apoptotic protein

  An anti-apoptotic protein overexpressed in macrophages to test whether it alters susceptibility to Shigella-triggered death.

  Aliases: B-cell lymphoma 2

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• caspase-1

  protease

  An inflammatory cysteine protease that is the central caspase analyzed for binding, activation, and apoptotic signaling in this work.

  Aliases: Casp-1

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• caspase-11

  protease

  A caspase protease tested in knockout macrophages for its relationship to Shigella-triggered cell death.

  Aliases: Casp-11

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• caspase-2

  protease

  A caspase protease used as a binding comparison against caspase-1 in the experiments.

  Aliases: Casp-2

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• caspase-3

  protease

  A caspase protease used as a binding comparison and knockout background in the study.

  Aliases: Casp-3

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• interleukin-1β

  cytokine

  A pro-inflammatory cytokine substrate whose cleavage is used as a readout of caspase-1 activity.

  Aliases: IL-1β

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• ipab

  protein

  A Shigella invasion plasmid antigen B protein examined here for binding to caspases in macrophage apoptosis.

  Aliases: invasion plasmid antigen B

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• macrophages

  cell type

  The immune cell type used to test susceptibility to Shigella-triggered apoptosis.

  Aliases: macrophage

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• p53

  tumor suppressor protein

  A tumor suppressor protein tested here through knockout macrophages as part of the apoptosis specificity analysis.

  Aliases: tumor protein p53

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• shigella-induced apoptosis

  apoptotic process

  Apoptotic cell death in macrophages triggered by Shigella infection.

  Aliases: Shigella-induced macrophage apoptosis

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• shigella infection

  infection

  Exposure of macrophages to Shigella bacteria, used as the infection context for the apoptosis assays.

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• signal transduction

  cell process

  Intracellular signaling cascades that transmit activation cues before caspase-1 engagement.

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review
• upstream caspases

  protein group

  Caspase activities positioned before caspase-1 in apoptotic signaling pathways.

  Aliases: caspases upstream of caspase-1

  mexicorea (qjvnbu8xg3) extractionAnonymous (12632b8b5f) review박진우 (dztg5apj7m) review뀨 (7c402c1b98) review

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