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Evolutionarily conserved developmental pathways

Programmed cell death - apoptosis - a common pathway for developmentally regulated cell death

Programmed cell death, or apoptosis, is the regulated elimination of cells that occurs naturally during the course of development, as well as in many pathological circumstances that require cell death for the benefit of the organism. This deliberate elimination of cells occurs in a morphologically distinct manner that suggests an active, gene-directed process. Investigation of the pathways involved in apoptosis provide a fascinating exercise in unraveling complex gene interactions.

There are at least four components in the apoptosis cascade. Homologs of Drosophila Reaper possess a conserved protein sequence called the "death domain." Expression or activation of death domain proteins initiates the apoptosis process. In an unknown fashion, death domain proteins activate cysteine proteases of the ICE/CED-3 family. These proteases target various enzymes, initiating a proteolytic cascade of key proteins involved in cell function, ultimately leading to cell death. A third component of the apoptosis cascade is a family of proteins that functions to inhibit ICE/CED-3 proteases. These inhibitors, serving to block apoptosis, are termed IAP proteins. They directly interact with ICE-like proteases. A fourth component in the apoptosis cascade consists of a family of proteins related to Bcl2. Bcl2 family members act by unknown mechanism(s) to counteract or expedite the apoptosis process.

Drosophila                        Homologs in other species ----------                        ----------------------------Reaper                            Mammalian: MORT1 (also called FADD), TRADD, and RIPHead involution defective         Mammalian: MORT1 (also called FADD), TRADD, and RIPGrim (See Reaper)                 Mammalian: MORT1 (also called FADD), TRADD, and RIPcaspase-1                         C. elegans: Ced-3                                   Mammalian: interleukin-1beta-converting enzyme (ICE) and CPP32Death related ced-3/Nedd2-like protein                                                                                                                  C. elegans: Ced-3                                   Mammalian: Caspase-8/FLICEDIAP1 and DIAP2 (See Reaper)      Baculovirus: protein p35                                  Mammalian: c-IAP1 and c-IAP2death executioner Bcl-2 homologue Mammalian: bcl-2 and bax and related family members

date revised: 24 DEC 96

Developmental Pathways conserved in Evolution

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