title: CPP32/Yama/apopain cleaves the catalytic component of DNA-dependent protein kinase in the holoenzyme.
abstract: DNA-dependent protein kinase (DNA-PK) is composed of a 460-kDa catalytic component (p460) and a DNA-binding component Ku protein. Immunoblot analysis after treatment of Jurkat cells with anti-Fas antibody demonstrated the cleavage of p460 concomitantly with an increase in CPP32/Yama/apopain activity. Recombinant CPP32/Yama/apopain specifically cleaved p460 in the DNA-PK preparation that had been purified from Raji cells into 230- and 160-kDa polypeptides, the latter of which was detected in anti-Fas-treated Jurkat cells. The regulatory component Ku protein was not significantly affected by CPP32/Yama/apopain. DNA-PK activity was decreased with the disappearance of p460 in the incubation of DNA-PK with CPP32/Yama/apopain. These results suggest that the catalytic component of DNA-PK is one of the target proteins for CPP32/Yama/apopain in Fas-mediated apoptosis.
authors.affiliation: Department of Pathological Biochemistry, Tokyo Medical and Dental University, Japan. hteraoka.pbc@mri1.mri.tmd.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Teraoka
authors.forename: Y
authors.initials: Y
authors.lastname: Yumoto
authors.forename: F
authors.initials: F
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Tsukada
authors.forename: A
authors.initials: A
authors.lastname: Suwa
authors.forename: M
authors.initials: M
authors.lastname: Enari
authors.forename: S
authors.initials: S
authors.lastname: Nagata
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D053148:Caspase 3; D020169:Caspases; D002384:Catalysis; D002417:Cattle; D003067:Coenzymes / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013379:Substrate Specificity; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D003067:Coenzymes; D004268:DNA-Binding Proteins; D004792:Enzyme Precursors; D009687:Nuclear Proteins; D004247:DNA; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases