Abstract
The Ku autoantigen/KARP-1 (Ku86 autoantigen related protein-1) plays an important role in the double-strand break repair of mammalian DNA as a DNA-binding component of DNA-dependent protein kinase (DNA-PK) complex. KARP-1 is differently transcribed from the human Ku86 autoantigen gene locus and it is implicated in the control of DNA-dependent protein kinase activity. We cloned rKAB1, a rat homolog of KAB1 (KARP-1 binding protein 1 of human) from a rat hippocampal cDNA library. rKAB1 mRNA was specifically expressed in the brain and the thymus. EGFP-tagged rKAB1 protein localized in cell nucleus and in the condensed chromosome during the mitotic cell division. We found that rKAB1 works as a protective protein against cell damage by oxidative stress.
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Gottlieb TM, Jackson SP: The DNA-dependent protein kinase: Requirement for DNA ends and association with Ku antigen. Cell 72: 131-142, 1993
Jeggo PA: DNA-PK: At the cross-roads of biochemistry and genetics. Mutat Res 384: 1-14, 1997
Nussenzweig A, Chen C, da Costa Soares V, Sanchez M, Sokol K, Nussenzweig MC, Li GC: Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature 382: 551-555, 1996
Zhu C, Bogue MA, Lim DS, Hasty P, Roth DB: Ku86-deficient mice exhibit severe combined immunodeficiency and defective processing of V(D)J recombination intermediates. Cell 86: 379-389, 1996
Gu Y, Jin S, Gao Y, Weaver DT, Alt FW: Ku70-deficient embryonic stem cells have increased ionizing radiosensitivity, defective DNA end-binding activity, and inability to support V(D)J recombination. Proc Natl Acad Sci USA 94: 8076-8081, 1997
Myung K, He DM, Lee SE, Hendrickson EA: KARP-1: A novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity. EMBO J 16: 3172-3184, 1997
Myung K, Braastad C, He DM, Hendrickson EA: KARP-1 is induced by DNA damage in a p53-and ataxia telangiectasia mutated-dependent fashion. Proc Natl Acad Sci USA 95: 7664-7669, 1998
Boveris A: Mitochondrial production of superoxide radical and hydrogen peroxide. Adv Exp Med Biol 75: 67-82, 1977
Badwey JA, Karnovsky ML: Active oxygen species and the functions of phagocytic leukocytes. Annu Rev Biochem 49: 695-726, 1980
Cao W, Carney JM, Duchon A, Floyd RA, Chevion M: Oxygen free radical involvement in ischemia and reperfusion injury to brain. Neurosci Lett 88: 233-238, 1988
Whittemore ER, Loo DT, Cotman CW: Exposure to hydrogen peroxide induces cell death via apoptosis in cultured rat cortical neurons. NeuroReport 5: 1485-1488, 1994
Whittemore ER, Loo DT, Watt JA, Cotman CW: A detailed analysis of hydrogen peroxide-induced cell death in primary neuronal culture. Neuroscience 67: 921-932, 1995
Dizdaroglu M, Nackerdien Z, Chao BC, Gajewski E, Rao G: Chemical nature of in vivo DNA base damage in hydrogen peroxide-treated mammalian cells. Arch Biochem Biophys 285: 388-390, 1991
Schraufstatter IU, Hyslop PA, Hinshaw DB, Spragg RG, Sklar LA, Cochrane CG: Hydrogen peroxide-induced injury of cells and its prevention by inhibitors of poly(ADP-ribose)polymerase. Proc Natl Acad Sci USA 83: 4908-4912, 1986
Zhang F, Xu S, Iadecola C: Time dependence of effect of nitric oxide synthase inhibition on cerebral ischemic damage. J Cereb Blood Flow Metab 15: 595-601, 1995
Suzuki T, Akaike N, Ueno K, Tanaka Y, Himori N: MAO inhibitors, clorgyline and lazabemide, prevent hydroxyl radical generation caused by brain ischemia/reperfusion in mice. Pharmacology 50: 357-362, 1995
Lancelot E, Callebert J, Revaud ML, Boulu RG, Plotkine M: Detection of hydroxyl radicals in rat striatum during transient focal cerebral ischemia: Possible implication in tissue damage. Neurosci Lett 197: 85-88, 1995
Globus MY, Busto R, Lin B, Schnippering H, Ginsberg MD: Detection of free radical activity during transient global ischemia and recirculation: Effects of intraischemic brain temperature modulation. J Neurochem 65: 1250-1256, 1995
Simonson SG, Zhang J, Canada AT, Su YF, Benveniste H, Piantadosi CA: Hydrogen peroxide production by monoamine oxidase during ischemia-reperfusion in the rat brain. J Cereb Blood Flow Metab 13: 125-134, 1993
Dawson VL, Dawson TM, Bartley DA, Uhl GR, Snyder SH: Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. J Neurosci 13: 2651-2661, 1993
Lafon-Cazal M, Pietri S, Culcasi M, Bockaert J: NMDA-dependent superoxide production and neurotoxicity. Nature 364: 535-537, 1993
Shackelford DA, Tobaru T, Zhang S, Zivin JA: Changes in expression of the DNA repair protein complex DNA-dependent protein kinase after ischemia and reperfusion. J Neurosci 19: 4727-4738, 1999
Woo RA, McLure KG, Lees-Miller SP, Rancourt DE, Lee PWK: DNA-dependent protein kinase acts upstream of p53 in response to DNA damage. Nature 394: 700-704, 1998
Chen J, Jin K, Chen M, Pei W, Kawaguchi K, Greenberg DA, Simon RP: Early detection of DNA strand breaks in the brain after transient focal ischemia: Implications for the role of DNA damage in apoptosis and neuronal cell death. J Neurochem 69: 232-245, 1997
Tobita M, Nagano I, Nakamura S, Itoyama Y, Kogure K: DNA single-strand breaks in postischemic gerbil brain detected by in situ nick translation procedure. Neurosci Lett 200: 129-132, 1995
Richardson SJ: Free radicals in the generation of Alzheimer's disease. Ann NY Acad Sci 695: 73-76, 1993
Olanow CW: An introduction to the free radical hypothesis in Parkinson's disease. Ann Neurol 32: S2-S9, 1992
Olanow CW: A radical hypothesis for neurodegeneration. Trends Neurosci 16: 439-444, 1993
Bellavite P: The superoxide-forming enzymatic system of phagocytes. Free Radical Biol Med 4: 225-261, 1988
Giulian D, Vaca K, Corpuz M: Brain glia release factors with opposing actions upon neuronal survival. J Neurosci 13: 29-37, 1993
Yamagata K, Andreasson KI, Kaufmann WE, Barnes CA, Worley PF: Expression of a mitogen-inducible cyclooxygenase in brain neurons: Regulation by synaptic activity and glucocorticoids. Neuron 11: 371-386, 1993
Irie Y, Yamagata K, Gan Y, Miyamoto K, Do E, Kuo CH, Taira E, Miki N: Molecular cloning and characterization of Amida, a novel protein which interacts with a neuron-specific immediate early gene product Arc, contains novel nuclear localization signals, and causes cell death in cultured cells. J Biol Chem 275: 2647-2653, 2000
Altschul SF, Gish W, Miller W, Myers EW: Basic local alignment search tool. J Mol Biol 215: 403-410, 1990
Linzer DI, Nathans D: Growth-related changes in specific mRNAs of cultured mouse cells. Proc Natl Acad Sci USA 80: 4271-4275, 1983
Robbins J, Dilworth SM, Laskey RA, Dingwall C: Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: Identification of a class of bipartite nuclear targeting sequence. Cell 64: 615-623, 1991
Moll U, Lau R, Sypes MA, Gupta MM, Anderson CW: DNA-PK, the DNA-activated protein kinase, is differentially expressed in normal and malignant human tissues. Oncogene 18: 3114-3126, 1999
Koike M, Matsuda Y, Mimori T, Harada YN, Shiomi N, Shiomi T: Chromosomal localization of the mouse and rat DNA double-strand break repair genes Ku p70 and Ku p80/XRCC5 and their mRNA expression in various mouse tissues. Genomics 38: 38-44, 1996
Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM: The E6 oncoprotein encoded by human papillomavirus type 16 and 18 promotes the degradation of p53. Cell 63: 1129-1136, 1990
Yin Y, Terauchi Y, Solomon GG, Aizawa S, Rangarajan PN, Yazaki Y, Kadowaki T, Barrett JC: Involvement of p85 in p53-dependent apoptotic response to oxidative stress. Nature 391: 707-710, 1998
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Do, E., Taira, E., Irie, Y. et al. Molecular cloning and characterization of rKAB1, which interacts with KARP-1, localizes in the nucleus and protects cells against oxidative death. Mol Cell Biochem 248, 77–83 (2003). https://doi.org/10.1023/A:1024157515342
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DOI: https://doi.org/10.1023/A:1024157515342