title: Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE.
abstract: Recent studies suggest that proteases of the interleukin 1-beta-converting enzyme (ICE)/ced-3 family are involved in initiating the active phase of apoptosis. Here we identify a novel protease resembling ICE (prICE) that is active in a cell-free system that reproduces the morphological and biochemical events of apoptosis. prICE cleaves the nuclear enzyme poly(ADP-ribose) polymerase (PARP) at a tetrapeptide sequence identical to one of two ICE sites in pro-interleukin-1-beta. However, prICE does not cleave purified pro-interleukin-1-beta, and purified ICE does not cleave PARP, indicating that the two activities are distinct. Inhibition of prICE abolishes all manifestations of apoptosis in the extracts including morphological changes, cleavage of PARP and production of an oligonucleosomal ladder. These studies suggest that prICE might be pivotal in initiating the active phase of apoptosis in vitro and in intact cells.
authors.affiliation: Department of Cell Biology and Anatomy, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
authors.forename: Y A
authors.initials: YA
authors.lastname: Lazebnik
authors.forename: S H
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: S
authors.initials: S
authors.lastname: Desnoyers
authors.forename: G G
authors.initials: GG
authors.lastname: Poirier
authors.forename: W C
authors.initials: WC
authors.lastname: Earnshaw
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D020170:Caspase 1; D002417:Cattle; D002474:Cell-Free System; D002645:Chickens; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D011498:Protein Precursors; C043830:interleukin 1 precursor; D011065:Poly(ADP-ribose) Polymerases; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D008666:Metalloendopeptidases; C089403:protease resembling ICE