title: Identification of the novel substrates for caspase-6 in apoptosis using proteomic approaches.
abstract: Apoptosis, programmed cell death, is a process involved in the development and maintenance of cell homeostasis in multicellular organisms. It is typically accompanied by the activation of a class of cysteine proteases called caspases. Apoptotic caspases are classified into the initiator caspases and the executioner caspases, according to the stage of their action in apoptotic processes. Although caspase-3, a typical executioner caspase, has been studied for its mechanism and substrates, little is known of caspase-6, one of the executioner caspases. To understand the biological functions of caspase-6, we performed proteomics analyses, to seek for novel caspase-6 substrates, using recombinant caspase-6 and HepG2 extract. Consequently, 34 different candidate proteins were identified, through 2-dimensional electrophoresis/MALDI-TOF analyses. Of these identified proteins, 8 proteins were validated with in vitro and in vivo cleavage assay. Herein, we report that HAUSP, Kinesin5B, GEP100, SDCCAG3 and PARD3 are novel substrates for caspase-6 during apoptosis.
authors.forename: Jin Hwa
authors.initials: JH
authors.lastname: Cho
authors.forename: Phil Young
authors.initials: PY
authors.lastname: Lee
authors.forename: Woo-Chan
authors.initials: WC
authors.lastname: Son
authors.forename: Seung-Wook
authors.initials: SW
authors.lastname: Chi
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Park
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Medical Proteomics Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 305-333, Korea sgpark@kribb.re.kr.
authors.forename: Sung Goo
authors.initials: SG
authors.lastname: Park
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053178:Caspase 6 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D040901:Proteomics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity
chemical_list: D061945:Caspase Inhibitors; D011994:Recombinant Proteins; D053178:Caspase 6