cell engineering vol vol chapter细胞工程卷卷.pdfVIP

1. CASPASE REGULATION AT THE MOLECULAR LEVEL HITTO KAUFMANN1+ AND MARTIN FUSSENEGGER2 * 1 Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3050, Australia 2Institute of Biotechnology, Swiss Federal Institute of Technology, ETH Hoenggerberg, HPT D74, CH-8093 Zurich, Switzerland. + Present Address: Boehringer Ingelheim Pharma GmbH Co. KG GFP BP, Birkendorfer Str. 65, D-88397 Biberach * Corresponding Author: Fax: +41 1 633 12 34 E-mail: fussenegger@biotech.biol.ethz.ch 1. Introduction Apoptosis or programmed cell death is an essential process required for precise embryonic development and tissue homeostasis in adult species. Programmed cell death is controlled by sequential action of a specific set of proteins which are conserved throughout multicellular organisms and convert death-inducing signal(s) into cell-disassembling biochemical processes. Molecular details of the apoptosis machinery first emerged from a genetic screen of the hermaphrodite nematode Caenorhabditis elegans which revealed the four global apoptosis regulators ced-3, ced-4, ced-9 and egl-1 (Metzstein et al., 1998). ced-3 encodes a member of the cystein-containing aspartate-specific proteases family known as “caspases”. ced-3-deficient C. elegans mutants were devoid of programmed cell death during development (Ellis and Horvitz 1986). Ced-4 is an activator of caspase-mediated cell death and nematodes lac