Apoptosis is a common mechanism among multicellular organisms to eliminate cells that are no longer needed or have become damaged. It is a morphologically and biochemically distinct form of cell death that can be triggered by a wide range of internal and external signals (for review see reference <sup>141 White E. Life, death, and the pursuit of apoptosis Genes Dev 1996 ;  10 : 1  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup>). The fundamental apoptosis signaling pathway has been highly conserved throughout evolution. Genetic screens in the nematode Caenorhabditis elegans have identified 3 genes (ced-9, ced-4 and ced-3) that resemble a basic apoptotic machinery that is also conserved in the mammalian system (for review see reference <sup>84 Metzstein M.M., Stanfield G.M., Horvitz H.R. Genetics of programmed cell death in C. elegans: Past, present and future Trends Genet 1998 ;  14 : 410

Cliccare qui per andare alla sezione Riferimenti</sup>). The antiapoptotic molecule CED-9 negatively regulates the activity of the proapoptotic molecule CED-4, which in turn activates the cysteine protease CED-3. Mammalian homologues of CED-9, CED-4, and CED-3 are Bcl-2, apoptopic protease-activating factor 1 (Apaf-1)<sup>150 Zou H., Henzel W.J., Liu X. , e al. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3 Cell 1997 ;  90 : 405  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> and the caspase protease family, respectively. EGL-1,<sup>23 Conradt B., Horvitz H.R. The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9 Cell 1998 ;  93 : 519  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup>, a homologue of the proapoptotic BH3 domain containing Bcl-2 family members, such as Bik, Bid, or Bad, is another proapoptotic molecule in C. elegans that was found to interact with CED-9, inhibiting its antiapoptotic activity and thereby setting the CED-4/CED-3 apoptosis machinery into motion.<sup>26 del Peso L., Gonzalez V.M., Nunez G. Caenorhabditis elegans EGL-1 disrupts the interaction of CED-9 with CED-4 and promotes CED-3 activation J Biol Chem 1998 ;  273 : 33495  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> The key molecules required for the execution of apoptosis in most systems seem to be the caspases, which cleave a variety of cellular substrates and thereby cause the characteristic morphology of apoptotic cells (rounded cells, condensed chromatin, susceptibility to phagocytosis). Caspases seem to have developed together with the development of multicellular organisms and can be found in nematodes, insects, and mammals. Even in the simple metazoan Hydra vulgaris apoptosis is accompanied with activation of caspases.<sup>21 Cikala M., Wilm B., Hobmayer , e al. Identification of caspases and apoptosis in the simple metazoan Hydra Curr Biol 1999 ;  9 : 959

Cliccare qui per andare alla sezione Riferimenti</sup> This article summarizes recent advances in the identification and the study of the caspases. The authors also discuss cell death mechanisms that are independent of these cysteine proteases.