Proteases to die for

These findings suggest that ced-4 is genetically and functionally sandwiched between the upstream death antagonist ced-9 and the downstream death mediator ced-3

Vincent Cryns; Junying Yuan

2008

Scholarcy highlights

  • Genetic studies of developmental PCD in C. elegans have identified two genes that are each required for the execution of cell death and one that inhibits cell death
  • The ability of ced-9 to inhibit ced-3-induced killing requires a functional ced-4 gene. These findings suggest that ced-4 is genetically and functionally sandwiched between the upstream death antagonist ced-9 and the downstream death mediator ced-3
  • Ectopic expression of ced-4 or ced-3 can induce apoptosis in mammalian cells that can be overcome by Bcl-2 or caspase inhibitors
  • Using yeast-two hybrid analyses or ectopic expression in mammalian cells, several groups have demonstrated that CED-4 can bind to CED-9, CED-3, or both simultaneously
  • CED-4 binding to CED-3 is mediated by a conserved amino-terminal protein interaction module, the socalled caspase-recruitment domain that is present in Apaf-1 and several caspases
  • FADD/ MORT1 provides the direct link between these activated death receptor complexes and the caspase proteolytic cascade, its role in TRAIL-induced apoptosis via DR4 and DR5 has been supported by some studies but not others
  • C-IAP1, c-IAP2, and XIAP have a conserved carboxy-terminal RING finger, zincbinding domain characteristic of the baculoviral inhibitors of apoptosis. Overexpression of these mammalian IAPs confers resistance to apoptotic cell death induced by a broad range of stimuli; protection against apoptosis requires the baculoviral IAP repeat domains but not the RING finger

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