title: Molecular cloning and pro-apoptotic activity of ICErelII and ICErelIII, members of the ICE/CED-3 family of cysteine proteases.
abstract: Cysteine proteases related to mammalian interleukin-1 beta-converting enzyme (ICE) and the nematode cell death abnormal ced-3 gene product have been implicated in the effector mechanism of apoptotic cell death. Two novel members of this new family of ICE/CED-3-related proteases, designated ICErel-II and ICErel-III, were cloned from human monocytic cells. Both were highly homologous to human ICE (52% identical) and CED-3 (25% identical) and both contained the absolutely conserved pentapeptide sequence Gln-Ala-Cys-Arg-Asp containing the catalytic cysteine residue. Other structural motifs that were comparable with ICE suggest that ICErel-II and ICErel-III are also synthesized as larger proenzymes which are proteolytically processed to form heterodimeric active enzymes. Pro-interleukin-1 beta processing activity could not be detected in cells transfected with ICErel-II or ICErel-III, but pro-domain-less truncated forms of ICErel-II and ICErel-III were capable of effectively inducing fibroblast apoptosis. ICErel-II and ICErel-III may, therefore, participate in proteolytic events culminating in the apoptotic death of human cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Quebec, Canada.
authors.forename: N A
authors.initials: NA
authors.lastname: Munday
authors.forename: J P
authors.initials: JP
authors.lastname: Vaillancourt
authors.forename: A
authors.initials: A
authors.lastname: Ali
authors.forename: F J
authors.initials: FJ
authors.lastname: Casano
authors.forename: D K
authors.initials: DK
authors.lastname: Miller
authors.forename: S M
authors.initials: SM
authors.lastname: Molineaux
authors.forename: T T
authors.initials: TT
authors.lastname: Yamin
authors.forename: V L
authors.initials: VL
authors.lastname: Yu
authors.forename: D W
authors.initials: DW
authors.lastname: Nicholson
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D020170:Caspase 1; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D003546:Cysteine Endopeptidases; D020170:Caspase 1