Interaction between DNA-dependent protein kinase and a novel protein, KIP.
DNA-dependent protein kinase (DNA-PKcs) is the only eukaryotic kinase activated by DNA ends. Mutation of DNA-PKcs results in murine severe combined immune deficiency in mice and radiation sensitivity. Both the immune and the radiation defects are due to a failure in double-strand break repair. Biochemical studies indicate that DNA-PKcs kinase activity is stimulated by the presence of the DNA end binding protein. Ku. Autophosphorylation of DNA-PKcs results in its inactivation. Based on these studies, DNA-PKcs is presumed to play a direct and important role in the repair of double-strand breaks, but the details of its role are quite unclear. We have done two-hybrid analysis of this entire protein to identify other proteins with which it interacts. Thus far, extensive analysis has only revealed one strong interaction that satisfies both high genetic and biochemical stringency. The interaction is with a novel human protein that has 26% amino acid identity with the phosphatase component, calcineurin B. We discuss the interaction of DNA-PKcs with this novel calcium-binding protein family member in the context of possible kinase-phosphatase regulation of DNA end joining.
Wu
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Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Lieber
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MR
D000328:Adult; D000595:Amino Acid Sequence; D034961:Antigens, Nuclear; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D004265:DNA Helicases; D004260:DNA Repair / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D000072200:Ku Autoantigen; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D034961:Antigens, Nuclear; C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C081647:high affinity DNA-binding factor, S cerevisiae; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen