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Turning ON Caspases with Genetics and Small Molecules
Filetype[PDF - 1.70 MB]


Details:
  • Pubmed ID:
    24974291
  • Pubmed Central ID:
    PMC4249682
  • Funding:
    DP1 MH099900/MH/NIMH NIH HHS/United States
    DP1MH099900/DP/NCCDPHP CDC HHS/United States
    F31 NS078959/NS/NINDS NIH HHS/United States
    R01 CA136779/CA/NCI NIH HHS/United States
    R01 CA136779/CA/NCI NIH HHS/United States
    R01 GM081051/GM/NIGMS NIH HHS/United States
    R01 GM081051/GM/NIGMS NIH HHS/United States
    R01 NS049488/NS/NINDS NIH HHS/United States
    R01 NS083872/NS/NINDS NIH HHS/United States
    R01NS049488/NS/NINDS NIH HHS/United States
    R01NS083872/NS/NINDS NIH HHS/United States
    T32 GM064337/GM/NIGMS NIH HHS/United States
  • Document Type:
  • Collection(s):
  • Description:
    Caspases, aspartate-specific cysteine proteases, have fate-determining roles in many cellular processes including apoptosis, differentiation, neuronal remodeling, and inflammation (for review, see Yuan & Kroemer, 2010). There are a dozen caspases in humans alone, yet their individual contributions toward these phenotypes are not well understood. Thus, there has been considerable interest in activating individual caspases or using their activity to drive these processes in cells and animals. We envision that such experimental control of caspase activity can not only afford novel insights into fundamental biological problems but may also enable new models for disease and suggest possible routes to therapeutic intervention. In particular, localized, genetic, and small-molecule-controlled caspase activation has the potential to target the desired cell type in a tissue. Suppression of caspase activation is one of the hallmarks of cancer and thus there has been significant enthusiasm for generating selective small-molecule activators that could bypass upstream mutational events that prevent apoptosis. Here, we provide a practical guide that investigators have devised, using genetics or small molecules, to activate specific caspases in cells or animals. Additionally, we show genetically controlled activation of an executioner caspase to target the function of a defined group of neurons in the adult mammalian brain.