Abstract

Martin Raft (University College London) opened the meeting, which was organized by Stan Korsmeyer (Washington University), Shigekazu Nagata (Osaka Bioscience Institute) and Andrew Wyllie (Edinburgh), by reviewing the history ofapoptosis as a field of study and then raising a number of pertinent questions that still need to be answered; for example, how do Bcl-2 protein family members regulate cell death and what is the role of individual death inducing caspase proteases and their target substrates? Raft presented evidence that caspases are involved in normal developmental cell deaths in addition to death by insult as the caspase inhibitor zVADfmk blocks neural tube closure in the chick embryo. He also provided further evidence for his theorems that all cells (except blastomeres) require extracellular signals for survival, and that all cells possess the required components to undergo apoptosis without de novo transcription. Raft summarized data demonstrating that single cell organisms such as Dictyostelium, trypanosomes and bacteria undergo programmed cell death. The role for proteases in programmed cell death in mammals was likened to the E. coli Lit protease which is activated by the head protein of bacteriophage T4 (through a proteolysis step) which in turn cleaves EF-Tu leading to cell death.

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