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Regulation of cell apoptosis by protein kinase c δ

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Abstract

The isoforms of the PKC family are activated in response to mitogenic stimuli, to inflammatory stimuli, and to stress and play important roles in a variety of cellular functions including apoptosis. PKCδ a member of the novel PKC subfamily, is actively involved in cell apoptosis in a stimulus and tissue specific manner; it both regulates the expression and function of apoptotic related proteins and is itself a target for caspases. Activation of PKCδ by various apoptotic stimuli results in the translocation of PKCδ to distinct cellular compartments such as mitochondria, golgi and nucleus, and the differential translocation contributes to its different effects. In addition, phosphorylation of PKCδ on distinct tyrosine residues and its association with specific apoptotic related proteins such as c-Abl, DNA-PK, p73 and lamin B are pivotal to its function in cell apoptosis. Recent findings on these aspects of the PKCδ cascades are the major focus of this review.

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References

  1. Kerr JFR, Wyllie AH, Currie AR. Apoptosis: A basic biological phenomenon with wide range implications in tissue kinetics. Br J Cancer 1972; 26: 239–257.

    Google Scholar 

  2. Strasser A, O'Connor L, Dixit VM. Apoptosis signaling. Annu Rev Biochem 2000; 69: 217–245.

    Google Scholar 

  3. Kroemer G. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med 1997; 3: 614–620.

    Google Scholar 

  4. Nunez G, Benedict MA, Hu Y, Inohara, N. Caspases: The proteases of the apoptotic pathway. Oncogene 1998; 17: 3237–3245.

    Google Scholar 

  5. Wajant H. The Fas signaling pathway: More than a paradigm. Science 2002; 296: 1635–1536.

    Google Scholar 

  6. Ashkenazi A, Dixit VM. Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 1999; 11: 255–260.

    Google Scholar 

  7. Salvesen GS, Dixit VM. Caspases: Intracellular signaling by proteolysis. Cell 1997; 91: 443–446.

    Google Scholar 

  8. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998; 281: 1309–1312.

    Google Scholar 

  9. Kuida K. Caspase-9. Int J Biochem Cell Biol 2000; 32: 121–124.

    Google Scholar 

  10. Kumar S. Mechanisms mediating caspase activation in cell death. Cell Death Differ 1999; 6: 1060–1066.

    Google Scholar 

  11. Sun XM, MacFarlane M, Zhuang J, Wolf BB, Green DR, Cohen GM. Distinct caspase cascades are initiated in receptormediated and chemical-induced apoptosis. J Biol Chem 1999; 274: 5053–5060.

    Google Scholar 

  12. Franklin RA, McCubrey JA. Kinases: Positive and negative regulators of apoptosis. Leukemia 2000; 14: 2019–2034.

    Google Scholar 

  13. Cross TG, Scheel-Toellner D, Henriquez NV, Deacon E, Salmon M, Lord JM. Serine/threonine protein kinases and apoptosis. Exp Cell Res 2000; 256: 34–41.

    Google Scholar 

  14. Kennedy SG, Wagner AJ, Conzen SD, et al. The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Gene Dev 2000; 11: 701–713.

    Google Scholar 

  15. Chen YR, Tan TH. The c-Jun N-terminal kinase pathway and apoptotic signaling. Int J Oncol 2000; 16: 651–662.

    Google Scholar 

  16. Wang Y. Regulation of cell death by the Abl tyrosine kinase. Oncogene 2000; 19: 5643–5650.

    Google Scholar 

  17. Whelan DHR, Parker PJ. Loss of protein kinase C function induces an apoptotic response. Oncogene 1998; 16: 1939–1944.

    Google Scholar 

  18. Heidkamp MC, Bayer AL, Martin JL, Samarel AM. Differential activation of mitogen-activated protein kinase cascades and apoptosis by protein kinase Cδ and δ in neonatal rat ventricular myocytes. Circ Res 2001; 89: 882–890.

    Google Scholar 

  19. Hug H, Sarre TF. Protein kinase C isoenzymes: Divergence in signal transductionδ Biochem J 1993; 291: 329–343.

    Google Scholar 

  20. Jaken, S. Protein kinase C isozymes and substrates. Curr Opin Cell Biol 1996; 8: 168–173.

    Google Scholar 

  21. Newton AC. Protein kinase C. Seeing two domains. Curr Biol 1995; 5: 973–976.

    Google Scholar 

  22. Le Good JA, Ziegler WH, Parekh DB, Alessi DR, Cohen P, Parker PJ. Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1. Science 1998; 281: 2042–2045.

    Google Scholar 

  23. Emoto Y, Kisaki H, Manome Y, Kharbanda S, Kufe D. Activation of protein kinase Cdelta in human myeloid leukemia cells treated with 1-beta-D-arabinofuranosylcytosine. Blood 1996; 87: 1990–1996.

    Google Scholar 

  24. Ono Y, Fujii T, Ogita K, Kikkawa U, Igarashi K, Nishizuka Y. Identification of three additional members of rat protein kinase C family: Delta-, epsilon-and zeta-subspecies. FEBS Lett 1987; 226: 125–128.

    Google Scholar 

  25. Gschwendt M. Protein kinase C δ. Eur J Biochem 1999; 259: 555–564.

    Google Scholar 

  26. Zhimin Lu, Liu D, Hornia A, Devonish W, Pagano M, Foster DA. Activation of protein kinase C triggers its ubiquitination and degradation. Mol Cell Biol 1998; 18: 839–845.

    Google Scholar 

  27. Lu Z, Hornia A, Jiang YW, Zang O, Ohno S, Foster DA. Tumor promotion by depleting cells of protein kinase Cδ. Mol Cell Biol 1997; 17: 3418–3428.

    Google Scholar 

  28. Watanabe T, Ono Y, Taniyama Y, et al. Cell division arrest induced by phorbol ester in CHO cells overexpressing protein kinase Cδ subspecies. Proc Natl Acad Sci USA 1992; 89: 10159–10163.

    Google Scholar 

  29. Miyamoto A, Nakayama K, Imaki H, et al. Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cδ. Nature 2002; 416: 865–869.

    Google Scholar 

  30. Illera VA, Perandones CE, Stunz LL, Mower DA, Jr., Ashman RF. Apoptosis in splenic B lymphocytes. Regulation by protein kinase C and IL-4. J Immunol 1993; 151: 2965–2973.

    Google Scholar 

  31. Lucas M, Sanchez-Margalet V. Protein kinase C involvement in apoptosis. Gen Pharmacol 1995; 265: 881–887.

    Google Scholar 

  32. Kazanietz MG. Novel “nonkinase” phorbol ester receptors: The C1 domain connection. Mol Pharmacol 2002; 61: 759–767.

    Google Scholar 

  33. Ruvolo PP, Deng X, Carr BK, May WS. A functional role for mitochondrial protein kinase Cδ in Bcl2 phosphorylation and suppression of apoptosis. J Biol Chem 1998; 273: 25436–25442.

    Google Scholar 

  34. Gubina E, Rinaudo MS, Szallasi Z, Blumberg PM, Mufson RA. Overexpression of protein kinase C isoform δ but not δ in human interleukin-3-dependent cells suppresses apoptosis and induces bcl-2 expression. Blood 1998; 91: 823–829.

    Google Scholar 

  35. Jamieson L, Carpenter L, Biden TJ, Fields AP. Protein kinase Cδ activity is necessary for Bcr-Abl-mediated resistance to drug-induced apoptosis. J Biol Chem 1999; 274: 3927–3930.

    Google Scholar 

  36. Datta R, Kojima H, Yoshida K, Kufe D. Caspase-3-mediated cleavage of protein kinase Cδ in induction of apoptosis. J Biol Chem. 1997; 272: 20317–20320.

    Google Scholar 

  37. Endo K, Oki E, Biedermann V, et al. Proteolytic cleavage and activation of protein kinase Cµ by caspase-3 in the apoptotic response of cells to 1-δ-D-arabinofuranosylcytosine and other genotoxic agents. J Biol Chem 2000; 275: 18476–18481.

    Google Scholar 

  38. Kaasinen SK, Goldsteins G, Alhonen L, Janne J, Koistinaho J. Induction and activation of protein kinase Cδ in hippocampus and cortex after kainic Acid treatment. Exp Neurol 2002; 176: 203–212.

    Google Scholar 

  39. Emoto Y, Manome Y, Meinhardt G, et al. Proteolytic activation of protein kinase Cδ by an ICE-like protease in apoptotic cells. EMBO J 1995; 14: 6148–6156.

    Google Scholar 

  40. Scheel-Toellner D, Pilling D, Akbar AN, et al. Inhibition of T cell apoptosis by IFN-δ rapidly reverses nuclear translocation of protein kinase C-delta. Eur J Immunol 1999; 8: 2603–2612.

    Google Scholar 

  41. Fukunaga M, Oka M, Ichihashi M, Yamamoto T, Matsuzaki H, Kikkawa U. UV-induced tyrosine phosphorylation of PKC delta and promotion of apoptosis in the HaCaT cell line. Biochem Biophys Res Commun 2001; 289: 573–579.

    Google Scholar 

  42. Denning MF, Wang Y, Nickoloff BJ, Wrone-Smith T. Protein kinase Cδ is activated by caspase-dependent proteolysis during ultraviolet radiation-induced apoptosis of human keratinocytes. J Biol Chem 1998; 273: 29995–30002.

    Google Scholar 

  43. Yuan ZM, Utsugisawa T, Ishiko T, et al. Activation of protein kinase Cδ by the c-Abl tyrosine kinase in response to ionizing radiation. Oncogene 1998; 16: 1643–1648.

    Google Scholar 

  44. Lee YJ, Soh JW, Dean NM, et al. Protein kinase Cδ overexpression enhances radiation sensitivity via extracellular regulated protein kinase 1/2 activation, abolishing the radiationinduced G(2)-M arrest. Cell Growth Differ 2002; 13: 237–246.

    Google Scholar 

  45. Reyland ME, Anderson SM, Matassa AA, Barzen KA, Quissell DO. Protein kinase C δ is essential for etoposide-induced apoptosis in salivary gland acinar cells. J Biol Chem 1999; 274: 19115–19123.

    Google Scholar 

  46. Dal Pra I, Whitfield JF, Chiarini A, Armato U. Increased activity of the protein kinase Cδ holoenzyme in the cytoplasmic particulate fraction precedes the activation of caspases in polyomavirus-transformed pyF111 rat fibroblasts exposed to calphostin C or topoisomerase-II inhibitors. Exp Cell Res 2000; 255: 171–183.

    Google Scholar 

  47. Cross T, Griffiths G, Deacon E, et al. PKCδ is an apoptotic lamin kinase. Oncogene 2000; 19: 2331–2337.

    Google Scholar 

  48. Godbout JP, Pesavento J, Hartman ME, Manson SR, Freund GG. Methylglyoxal enhances cisplatin-induced cytotoxicity by activating protein kinase Cδ. J Biol Chem 2002; 277: 2554–2561.

    Google Scholar 

  49. Majumder PK, Mishra NC, Sun X, et al. Targeting of protein kinase Cδ to mitochondria in the oxidative stress response. Cell Growth Differ 2001; 129: 465–470.

    Google Scholar 

  50. Konishi H, Yamauchi E, Taniguchi H, et al. Phosphorylation sites of protein kinase Cδ inH2O2-treated cells and its activation by tyrosine kinase in vitro. Proc Natl Acad Sci USA 2001; 98: 6587–6592.

    Google Scholar 

  51. Anantharam V, Kitazawa M, Wagner J, Kaul S, Kanthasamy AG. Caspase-3-dependent proteolytic cleavage of protein kinase Cδ is essential for oxidative stress-mediated dopaminergic cell death after exposure to methylcyclopentadienyl manganese tricarbonyl. J Neurosci 2002; 22: 1738–1751.

    Google Scholar 

  52. Kajimoto T, Ohmori S, Shirai Y, Sakai N, Saito N. Subtypespecific translocation of the δ subtype of protein kinase C and its activation by tyrosine phosphorylation induced by ceramide in HeLa cells. Mol Cell Biol 2001; 21: 1769–1783.

    Google Scholar 

  53. Pongracz, J, Webb P. Wang K. Deacon E. Lunn OJ, Lord JM. Spontaneous neutrophil apoptosis involves caspase 3-mediated activation of protein kinase C-δ. J Biol Chem 1999; 274: 37329–37334.

    Google Scholar 

  54. Khwaja A, Tatton L. Caspase-mediated proteolysis and activation of protein kinase Cδ play a central role in neutrophil apoptosis. Blood 1999; 94: 291–301.

    Google Scholar 

  55. Fujii T, Garcia-Bermejo ML, Bernabo JL, et'al. Involvement of protein kinase C δ in phorbol ester-induced apoptosis in LNCaP prostate cancer cells. Lack of proteolytic cleavage of PKCδ. J Biol Chem 2000; 275: 7574–7582.

    Google Scholar 

  56. Majumder PK, Pandey P, Sun X, et al. Mitochondrial translocation of protein kinase C delta in phorbol ester-induced cytochrome c release and apoptosis. J Biol Chem 2000; 275: 21793–21796.

    Google Scholar 

  57. Li L, Lorenzo PS, Bogi K, Blumberg PM, Yuspa SH. Protein kinase Cδ targets mitochondria, alters mitochondrial membrane potential, and induces apoptosis in normal and neoplastic keratinocytes when overexpressed by an adenoviral vector. Mol Cell Biol 1999; 19: 8547–8558.

    Google Scholar 

  58. Shizukuda Y, Reyland ME, Buttrick. PM Protein kinase Cδ modulates apoptosis induced by hyperglycemia in adult ventricular myocytes. Am J Physiol Heart Circ Physiol 2002; 282: H1625–634.

    Google Scholar 

  59. Carpenter L, Cordery D, Biden TJ. Inhibition of protein kinase Cδ protects rat INS-1 cells against interleukin-1 δ and streptozotocin-induced apoptosis. Diabetes 2002; 51: 317–324.

    Google Scholar 

  60. Datta R, Banach D, Kojima H, et al. Activation of the CPP32 protease in apoptosis induced by 1-beta-D arabinofuranosylcytosine and other DNA-damaging agents. Blood 1996; 88: 1936–1943.

    Google Scholar 

  61. Sun X, Wu F, Datta R, Kharbanda S, Kufe D. Interaction between protein kinase C delta and the c-Abl tyrosine kinase in the cellular response to oxidative stress. J Biol Chem 2000; 275: 7470–7473.

    Google Scholar 

  62. Chen N, Ma W, Huang C, Dong Z. Translocation of protein kinase Cδ and protein kinase Cδ to membrane is required for ultraviolet B-induced activation of mitogen-activated protein kinases and apoptosis. J Biol Chem 1999; 274: 15389–15394.

    Google Scholar 

  63. Matassa AA, Carpenter L, Biden TJ, Humphries MJ, Reyland ME. PKCδ is required for mitochondrial-dependent apoptosis in salivary epithelial cells. J Biol Chem 2001; 276: 29719–29728.

    Google Scholar 

  64. Mandil R, Ashkenazi E, Blass M, et al. Protein kinase Cδ and protein kinase Cδ play opposite roles in the proliferation and apoptosis of glioma cells. Cancer Res 2001; 61: 4612–4619.

    Google Scholar 

  65. Blass M, Kronfeld I, Kazimirsky G, Blumberg PM, Brodie C. Tyrosine phosphorylation of protein kinase Cδ is essential for its apoptotic effect in response to etoposide. Mol Cell Biol 2002; 22: 182–195.

    Google Scholar 

  66. Kilpatrick LE, Lee JY, Haines KM, Campbell DE, Sullivan KE, Korchak HM. A role for PKCδ and PI 3-kinase in TNFalpha-mediated antiapoptotic signaling in the human neutrophil. Am J Physiol Cell Physiol 2002; 283: C48–57.

    Google Scholar 

  67. Peluso JJ, Pappalardo A, Fernandez G. Basic fibroblast growth factor maintains calcium homeostasis and granulosa cell viability by stimulating calcium efflux via a PKC δ-dependent pathway. Endocrinology 2001; 142: 4203–4211.

    Google Scholar 

  68. Wert MM, Palfrey HC. Divergence in the anti-apoptotic signaling pathways used by nerve growth factor and basic fibroblast growth factor (bFGF) in PC12 cells: Rescue by bFGF involves protein kinase Cδ. Biochem J 2000; 352: 175–182.

    Google Scholar 

  69. Jun CD, Oh CD, Kwak HJ, et al. Overexpression of protein kinase C isoforms protectsRAW264.7 macrophages from nitric oxide-induced apoptosis: Involvement of c-Jun N-terminal kinase/stress-activated protein kinase, p38 kinase, and CPP-32 protease pathways. J Immunol 1999; 162: 3395–3401.

    Google Scholar 

  70. Zrachia A, Dobroslav M, Blass M, et al. Infection of glioma cells with Sindbis virus induces selective activation and tyrosine phosphorylation of protein kinase Cδ. Implications for Sindbis virus-induced apoptosis. J Biol Chem 2002; 277: 23693–23701.

    Google Scholar 

  71. Mochly-Rosen D, Gordon AS. Anchoring proteins for protein kinase C: Means for isozyme selectivity. FASEB J 1998; 12: 35–42.

    Google Scholar 

  72. Denning MF, Wang Y, Tibudan S, Alkan S, Nickoloff BJ, Qin JZ. Caspase activation and disruption of mitochondrial membrane potential during UV radiation induced apoptosis of human keratinocytes requires activation of protein kinase C. Cell Death Differ 2002; 9: 40–52.

    Google Scholar 

  73. Bertho N, Blancheteau VM, Setterblad N, et al. MHC class II-mediated apoptosis of mature dendritic cells proceeds by activation of the protein kinase Cδ isoenzyme. Int Immunol 2002; 14: 935–942.

    Google Scholar 

  74. Ghayur T, Hugunin M, Talanian RV, et al. Proteolytic activation of protein kinase Cδ by an ICE/CED 3-like protease induces characteristics of apoptosis. J Exp Med 1996; 184: 2399–2404.

    Google Scholar 

  75. Basu A, Woolard MD, Johnson CL. Involvement of protein kinase Cδ in DNA damage-induced apoptosis. Cell Death Differ 2001; 8: 899–908.

    Google Scholar 

  76. Basu A, Akkaraju GR. Regulation of caspase activation and cis-diamminedichloroplatinum(II)-induced cell death by protein kinase C. Biochemistry 1999; 38: 4245–4251.

    Google Scholar 

  77. Park IC, Park MJ, Hwang CS, et al. Mitomycin C induces apoptosis in a caspases-dependent and Fas/CD95-independent manner in human gastric adenocarcinoma cells. Cancer Lett 2000; 158: 125–132.

    Google Scholar 

  78. Martins LM, Kottke TJ, Kaufmann SH, Earnshaw WC. Phosphorylated forms of activated caspases are present in cytosol from HL-60 cells during etoposide-induced apoptosis. Blood 1998; 92: 3042–3049.

    Google Scholar 

  79. Cardone MH, Roy N, Stennicke HR, et al. Regulation of cell death protease caspase-9 by phosphorylation. Science 1998; 282: 1318–1321.

    Google Scholar 

  80. Sakurai Y, Onishi Y, Tanimoto Y, Kizaki H. Novel protein kinase Cδ isoform insensitive to caspase-3. Biol Pharm Bull 2001; 24: 973–937.

    Google Scholar 

  81. Li W, Mischak H, Yu JC, et al. Tyrosine phosphorylation of protein kinase Cδ in response to its activation. J Biol Chem 1994; 269: 2349–2352.

    Google Scholar 

  82. Song JS, Swann PG, Szallasi Z, Blank U. Blumberg PM, Rivera J. Tyrosine phosphorylation-dependent and-independent associations of protein kinase C-δ with Src family kinases in the RBL-2H3 mast cell line: Regulation of Src family kinase activity by protein kinase C-δ. Oncogene 1998; 16: 3357–3368.

    Google Scholar 

  83. Brodie C, Bogi K, Acs P, Lorenzo PS, Baskin L, Blumberg PM. Protein kinase Cδ (PKCdelta) inhibits the expression of glutamine synthetase in glial cells via the PKCδ regulatory domain and its tyrosine phosphorylation. J Biol Chem 1998; 273: 30713–30718.

    Google Scholar 

  84. Kronfeld I, Kazimirsky G, Lorenzo PS, Garfield SH, Blumberg PM, Brodie C. Phosphorylation of PKCδ on distinct tyrosine residues regulates specific cellular functions. J Biol Chem 2000; 275: 35491–35498.

    Google Scholar 

  85. Denning MF, Dlugosz AA, Threadgill DW, Magnuson T, Yuspa SH. Activation of the epidermal growth factor receptor signal transduction pathway stimulates tyrosine phosphorylation of protein kinase Cδ. J Biol Chem 1996; 271: 5325–5331.

    Google Scholar 

  86. Li W, Jiang YX, Zhang J, et al. Protein kinase Cδ is an important signaling molecule in insulin-like growth factor receptor-mediated cell transformation. Mol Cell Biol 1998; 18: 5888–5898.

    Google Scholar 

  87. Joseloff E, Cataisson C, Aamodt H, et al. Src family kinases phosphorylate protein kinase Cδ on tyrosine residues and modify the neoplastic phenotype of skin keratinocytes. J Biol Chem 2002; 277: 12318–12323.

    Google Scholar 

  88. Blake RA, Garcia-Paramio P, Parker PJ, Courtneidge SA. Src promotes PKCδ degradation. Cell Growth Differ 1999; 10: 231–241.

    Google Scholar 

  89. Kumar S, Bharti A, Mishra NC, et al. Targeting of the c-Abl tyrosine kinase to mitochondria in the necrotic cell death response to oxidative stress. J Biol Chem 2001; 276: 17281–17285.

    Google Scholar 

  90. Yuan ZM, Shioya H, Ishiko T, et al. p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage. Nature 1999; 399: 814–817.

    Google Scholar 

  91. Ren J, Datta R, Shioya H, et al. p73δ is regulated by the protein kinase Cδ catalytic fragment generated in the apoptotic response to DNA damage. J Biol Chem 2002; (in press).

  92. Kharbanda S, Bharti A, Pei D, et al. The stress response to ionizing radiation involves c-Abl-dependent phosphorylation of SHPTP1. Proc Natl Acad Sci USA 1996; 93: 6898–6901.

    Google Scholar 

  93. Yoshida K, Kufe D. Negative regulation of the SHPTP1 protein tyrosine phosphatase by protein kinase Cδ in response to DNA damage. Mol Pharmacol 2001; 60: 1431–1438.

    Google Scholar 

  94. Chen Z, Gibson TB, Robinson F, et al. MAP kinases. Chem Rev 2001; 101: 2449–2476.

    Google Scholar 

  95. Reyland ME, Barzen KA, Anderson SM, Quissell DO, Matassa AA. Activation of PKC is sufficient to induce an apoptotic program in salivary gland acinar cells. Cell Death Differ 2000; 7: 1200–1209.

    Google Scholar 

  96. Mitsutake N, Namba H, Shklyaev SS, et al. PKCδ mediates ionizing radiation-induced activation of c-Jun NH(2)-terminal kinase through MKK7 in human thyroid cells. Oncogene 2001; 20: 989–996.

    Google Scholar 

  97. Zhong M, Lu Z, Foster DA. DownregulatingPKCδ provides a PI3K/Akt-independent survival signal that overcomes apoptotic signals generated by c-Src overexpression. Oncogene 2002; 21: 1071–1078.

    Google Scholar 

  98. Zhou O, Zhao J, Stout JG, Luhm RA, Wiedmer T, Sims PJ. Molecular cloning of human plasma membrane phospholipid scramblase. Aprotein mediating transbilayer movement of plasma membrane phospholipids. J Biol Chem 1997; 272: 18240–18244.

    Google Scholar 

  99. Frasch SC, Henson PM, Kailey JM, et al. Regulation of phospholipid scramblase activity during apoptosis and cell activation by protein kinase Cδ. J Biol Chem 2000; 275: 23065–23073.

    Google Scholar 

  100. Sumitomo M, Ohba M, Asakuma J, et al. Protein kinase Cδ amplifies ceramide formation via mitochondrial signaling in prostate cancer cells. J Clin Invest 2002; 109: 827–836.

    Google Scholar 

  101. Smith GCM, Jackson SP. The DNA-dependent protein kinase. Genes & Dev. 1999; 13: 916–934.

    Google Scholar 

  102. Kharbanda S, Pandey P, Jin S, et al. Functional interaction of DNA-PK and c-Abl in response to DNA damage. Nature 1997; 386: 732–735.

    Google Scholar 

  103. Bharti A, Kraeft SK, Gounder M, et al. Inactivation of DNA-dependent protein kinase by protein kinase Cδ: Implications for apoptosis. Mol Cell Biol 1998; 18: 6719–6728.

    Google Scholar 

  104. Kaufmann SH. Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs: A cautionary note. Cancer Res 1989; 49: 5870–5878.

    Google Scholar 

  105. Peter M, Nakagawa J, Doree M, Labbe JC, Nigg EA. In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase. Cell 1990; 61: 591–602.

    Google Scholar 

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Brodie, C., Blumberg, P.M. Regulation of cell apoptosis by protein kinase c δ. Apoptosis 8, 19–27 (2003). https://doi.org/10.1023/A:1021640817208

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