Programmed Cell Death in Animal Development

We summarize what has been learned about the molecular mechanism of programmed cell death and some of the intracellular proteins that control it

Michael D Jacobson; Miguel Weil; Martin C Raff

2004

Scholarcy highlights

  • Kerr, Wyllie, and Currie marshalled morphological evidence from studies of their own and of others to draw a clear distinction between the cell deaths that occur in both animal development and tissue homeostasis, as well as in some pathological states, and the pathological cell deaths that occur at the center of acute lesions such as trauma and ischemia
  • By contrast, when cells die during normal development or tissue homeostasis, or at the periphery of acute lesions, they usually shrink and condense, and the organelles and plasma membrane retain their integrity in a process Kerr and his colleagues named apoptosis
  • Because apoptotic cell deaths usually look so similar from tissue to tissue and animal to animal, Kerr and his colleagues proposed that these deaths reflect the operation of an active, intracellular death program that can be activated or inhibited by a variety of physiological or pathological environmental stimuli
  • It took almost another 20 years, before the idea that animal cells have a built-in death, or suicide, program became generally accepted, largely through genetic studies in the nematode Caenorhabditis elegans that identified genes that seem dedicated to the death program and its control, and through the finding that some of these genes were homologous to mammalian genes
  • The Death Program and Its Intracellular Control There has been spectacular progress in the past few years in understanding the intracellular mechanism of programmed cell death and its control, reflected in the flood of reviews celebrating this success. Rather than covering this ground again, we focus on some of the evidence that supports the following four propositions concerning the intracellular death program: its protein components are constitutively expressed in all nucleated animal cells, its execution seems to involve a proteolytic cascade, its activation is controlled by a family of dedicated intracellular regulatory proteins, and its activation during development may often be controlled transcriptionally
  • There is one suicide program in some strains of E. coli that works much like programmed cell death in animal cells in that it is based on a constitutively expressed proteolytic enzyme, which is activated in response to infection by a T4 phage

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