96-30362 Wyche Programmed cell death is a normal part of animal development, is actively controlled by specific gene products, and is an event that occurs in various cells in the embryo and in adults. Programmed cell death, or apoptosis, can be induced in various cultured cell types by chemical and by physical treatment. Yet little is known about the molecular mechanism of apoptosis. This is partly caused by the fact that the positive and negative regulators of apoptosis are as yet unknown and partly to the lack of suitable mutants in the apoptotic signaling pathway. The objectives of this proposal are: a) isolation of chemically-resistant apoptosis cell variants from a human cell line (HL-60) and classification of the variants into complementation groups; b) identification of sequential cellular changes, structurally and biochemically, that are specifically associated with early progression of chemically-induced cell apoptosis; d) characterization of specific events leading to the activation of proteases as well as alterations in protein and DNA target sites in apoptotic cells and their variants. These studies should lead to the construction of the apoptotic signaling pathway and to insights into the relationship between apoptosis regulatory gene products and to specific events in the apoptotic signaling pathway. %%% Programmed cell death is a normal part of animal development, is actively controlled by specific gene products, and is an event that occurs in various cells in the embryo and in adults. Programmed cell death, or apoptosis, can be induced in various cultured cell types by chemical and by physical treatment. Yet little is known about the molecular mechanism of apoptosis. ***
