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CDK11p58 protein kinase activity is associated with Bcl-2 down-regulation in pro-apoptosis pathway

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Abstract

CDK11p58, a G2/M-specific protein kinase, has been shown to be associated with apoptosis in many cell lines, with largely unknown mechanisms. Our previous study proved that CDK11p58-enhanced cycloheximide (CHX)-induced apoptosis in SMMC-7721 hepatocarcinoma cells. Here we report for the first time that ectopic expression of CDK11p58 down-regulates Bcl-2 expression and its Ser70, Ser87 phosphorylation in CHX-induced apoptosis in SMMC-7721 cells. Overexpression of Bcl-2 counteracts the pro-apoptotic activity of CDK11p58. Furthermore, we confirm that the kinase activity of CDK11p58 is essential to the down-regulation of Bcl-2 as well as apoptosis. Taken together, these results demonstrate that CDK11p58 down-regulates Bcl-2 in pro-apoptosis pathway depending on its kinase activity, which elicits survival signal in hepatocarcinoma cells.

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References

  1. Ellis RE, Yuan JY, Horvitz HR (1991) Mechanisms and functions of cell death. Annu Rev Cell Biol 7:663–698

    Article  PubMed  CAS  Google Scholar 

  2. Williams GT, Smith CA (1993) Molecular regulation of apoptosis: genetic controls on cell death. Cell 74:777–779

    Article  PubMed  CAS  Google Scholar 

  3. Ashkenazi A, Dixit VM (1998) Death receptors: signaling and modulation. Science 281:1305–1308

    Article  PubMed  CAS  Google Scholar 

  4. Evan G, Littlewood T (1998) A matter of life and cell death. Science 281:1317–1322

    Article  PubMed  CAS  Google Scholar 

  5. Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281:1322–1326

    Article  PubMed  CAS  Google Scholar 

  6. Oltvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619

    Article  PubMed  CAS  Google Scholar 

  7. Li P, Nijhawan D, Budihardjo I et al (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479–489

    Article  PubMed  CAS  Google Scholar 

  8. Zou H, Henzel WJ, Liu X et al (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90:405–413

    Article  PubMed  CAS  Google Scholar 

  9. Breitschopf K, Haendeler J, Malchow P et al (2000) Prottranslational modification of Bcl-2 facilitates its proteasome-dependent degradation: molecular characterization of the involved signaling pathway. Mol Cell Biol 20:1886–1896

    Article  PubMed  CAS  Google Scholar 

  10. Ito T, Deng X, Carr B et al (1997) Bcl-2 phosphorylation required for anti-apoptosis function. J Biol Chem 272:11671–11673

    Article  PubMed  CAS  Google Scholar 

  11. Weil M, Jacobson MD, Coles HS et al (1996) Constitutive expression of the machinery for programmed cell death. J Cell Biol 133:1053–1059

    Article  PubMed  CAS  Google Scholar 

  12. Shi L, Nishioka WK, Th’ng J et al (1994) Premature p34cdc2 activation required for apoptosis. Science 263:1143–1145

    Article  PubMed  CAS  Google Scholar 

  13. Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81:323–330

    Article  PubMed  CAS  Google Scholar 

  14. Lahti JM, Xiang J, Heath LS et al (1995) PITSLRE protein kinase activity is associated with apoptosis. Mol Cell Biol 15:1–11

    PubMed  CAS  Google Scholar 

  15. Cai MM, Zhang SW, Zhang S et al (2002) Different effects of p58PITSLRE on the apoptosis induced by etoposide, cycloheximide and serum-withdrawal in human hepatocarcinoma cells. Mol Cell Biochem 238:49–55

    Article  PubMed  CAS  Google Scholar 

  16. Zhang S, Cai M, Zhang S et al (2002) Interaction of p58(PITSLRE), a G2/M-specific protein kinase, with cyclin D3. J Biol Chem 277:35314–35322

    Article  PubMed  CAS  Google Scholar 

  17. Tan KO, Tan KM, Chan SL et al (2001) MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains. J Biol Chem 276:2802–2807

    Article  PubMed  CAS  Google Scholar 

  18. Li Z, Wang H, Zong H et al (2005) Downregulation of beta1,4-galactosyltransferase 1 inhibits CDK11(p58)-mediated apoptosis induced by cycloheximide. Biochem Biophys Res Commun 327:628–636

    Article  PubMed  CAS  Google Scholar 

  19. Yin XM, Oltvai ZN, Korsmeyer SJ (1994) BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature 369:321–323

    Article  PubMed  CAS  Google Scholar 

  20. Tschopp J, Thome M, Hofmann K et al (1998) The fight of viruses against apoptosis. Curr Opin Genet Dev 8:82–87

    Article  PubMed  CAS  Google Scholar 

  21. Yang E, Zha J, Jockel J et al (1995) Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell 80:285–291

    Article  PubMed  CAS  Google Scholar 

  22. Sawada M, Nakashima S, Banno Y et al (2006) Influence of Bax or Bcl-2 overexpression on the ceramide-dependent apoptosis pathway in glioma cells. Oncogene 25:7440

    Article  CAS  Google Scholar 

  23. Armstrong RC, Aja T, Xiang J et al (1996) Fas-induced activation of the cell death-related protease CPP32 Is inhibited by Bcl-2 and by ICE family protease inhibitors. J Biol Chem 271:16850–16855

    Article  PubMed  CAS  Google Scholar 

  24. Lamothe B, Aggarwal BB (2002) Ectopic expression of Bcl-2 and Bcl-xL inhibits apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL) through suppression of caspases-8, 7, and 3 and BID cleavage in human acute myelogenous leukemia cell line HL-60. J Interferon Cytokine Res 22:269–279

    Article  PubMed  CAS  Google Scholar 

  25. Cornelis S, Bruynooghe Y, Denecker G et al (2000) Identification and characterization of a novel cell cycle-regulated internal ribosome entry site. Mol Cell 5:597–605

    Article  PubMed  CAS  Google Scholar 

  26. Xiang J, Lahti JM, Grenet J et al (1994) Molecular cloning and expression of alternatively spliced PITSLRE protein kinase isoforms. J Biol Chem 269:15786–15794

    PubMed  CAS  Google Scholar 

  27. Zong H, Li Z, Liu L et al (2005) Cyclin-dependent kinase 11(p58) interacts with HBO1 and enhances its histone acetyltransferase activity. FEBS Lett 579:3579–3588

    Article  PubMed  CAS  Google Scholar 

  28. Hockenbery D, Nunez G, Milliman C et al (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348:334–336

    Article  PubMed  CAS  Google Scholar 

  29. Zhu W, Cowie A, Wasfy GW et al (1996) Bcl-2 mutants with restricted subcellular location reveal spatially distinct pathways for apoptosis in different cell types. Embo J 15:4130–4141

    PubMed  CAS  Google Scholar 

  30. Jin Z, May WS, Gao F et al (2006) Bcl2 suppresses DNA repair by enhancing c-Myc transcriptional activity. J Biol Chem 281:14446–14456

    Article  PubMed  CAS  Google Scholar 

  31. Beyaert R, Kidd VJ, Cornelis S et al (1997) Cleavage of PITSLRE kinases by ICE/CASP-1 and CPP32/CASP-3 during apoptosis induced by tumor necrosis factor. J Biol Chem 272:11694–11697

    Article  PubMed  CAS  Google Scholar 

  32. Chen C, Yan J, Sun Q et al (2006) Induction of apoptosis by p110C requires mitochondrial translocation of the proapoptotic BCL-2 family member BAD. FEBS Lett 580:813–821

    Article  PubMed  CAS  Google Scholar 

  33. Thomas A, Giesler T, White E (2000) p53 mediates bcl-2 phosphorylation and apoptosis via activation of the Cdc42/JNK1 pathway. Oncogene 19:5259–5269

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Gene Research Center, Shanghai Medical College of Fudan University, Shanghai, 200032, P.R. China

    Xiaojing Yun, Yihong Wu, Luyang Yao, Hongliang Zong, Yi Hong, Jianhai Jiang, Junwu Yang, Zhou Zhang & Jianxin Gu

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  1. Xiaojing Yun
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  2. Yihong Wu
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  3. Luyang Yao
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  4. Hongliang Zong
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  5. Yi Hong
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  6. Jianhai Jiang
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  7. Junwu Yang
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  8. Zhou Zhang
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  9. Jianxin Gu
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Correspondence to Jianxin Gu.

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Yun, X., Wu, Y., Yao, L. et al. CDK11p58 protein kinase activity is associated with Bcl-2 down-regulation in pro-apoptosis pathway. Mol Cell Biochem 304, 213–218 (2007). https://doi.org/10.1007/s11010-007-9502-x

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  • DOI: https://doi.org/10.1007/s11010-007-9502-x

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