BIOCHEMICAL EVENTS IN NATURALLY-OCCURRING FORMS OF CELL-DEATH

Several molecular elements of programmed cell death and apoptosis have recently been revealed. The function of gene products which deliver t he lethal 'hit' is still not known. Well-characterized and newly disco vered cell surface structures (e.g. antigen receptors, FAS/APO-1), as well as transcriptional factors (steroid receptor, c-myc, P53, retinob lastoma protein and others), have been implicated in the initiation of the death pathway. Negative regulators of the process (ced-9 gene pro duct in programmed death of cells in Chaenorhabditis elegans and bcl-2 protein in apoptosis) have been described. Biochemical mechanisms res ponsible for the silent nature of natural deaths of cells include thei r rapid engulfment (mainly through integrin receptors), transglutamina se-catalyzed cross-linking of cellular proteins, and fragmentation of DNA. Several lines of evidence suggest that distinct molecular mechani sms may operate in various forms of natural cell death.