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Cell cycle and activation of CK2

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Abstract

Casein kinase 2 (CK2) is a highly conserved and ubiquitous eukaryotic Ser/Thr protein kinase. Genetic, biochemical, and cell biological studies have indicated the involvement of this enzyme in the control of cell proliferation and in signal transduction. The regulation of CK2 is not well defined, and it has been considered a constitutively non-regulated protein kinase. However, we show that CK2 activation occurred during the progression of cell cycle in response to FBS stimuli of G0 arrested cells. Importantly, we show that as the downstream target for CK2, the phosphorylation of eukaryotic translation-initiation factor eIF5 by CK2 may play a critical role in cell cycle progression. We find that eIF5 is associated with CK2 when the kinase activity is at the highest level in vivo, and is phosphorylated at Ser389 and Ser390 by CK2. Expression of eIF5 mutants that lack those phosphorylation sites reveals that these mutants have a dominant-negative effect on phosphorylation of endogenous eIF5, as well as a significant reduction in the formation of the mature complex, in the growth rate, and the expression of cell cycle-regulated proteins. Also, a pool of CK2 translocates into the nuclear fraction following its activation during the progression of the cell cycle. Consistent with these findings, we report that CK2 may be involved in the regulation of cell cycle progression through the phosphorylation of a key molecule for translation initiation and of nuclear substrates upon activation of CK2 by itself.

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Abbreviations

APC:

Adenomatous polyposis coli

CK2:

Casein kinase 2

DMEM:

Dulbecco’s modified Eagle’s medium

eIF5:

Eukaryotic translation initiation factor 5

FBS:

Fetal bovine serum

References

  1. Ahmed K, Gerber DA, Cochet C (2002) Joining the cell survival squad: an emerging role for protein kinase CK2. Trends Cell Biol 12:226–230. doi:10.1016/S0962-8924(02)02279-1

    Article  PubMed  CAS  Google Scholar 

  2. Guerra B, Issinger OG (1999) Protein kinase CK2 and its role in cellular proliferation, development and pathology. Electrophoresis 20:391–408. doi :10.1002/(SICI)1522-2683(19990201)20:2≤391::AID-ELPS391≥3.0.CO;2-N

    Article  PubMed  CAS  Google Scholar 

  3. Meggio F, Pinna LA (2003) One-thousand-and-one substrates of protein kinase CK2. FASEB J 17:349–368. doi:10.1096/fj.02-0473rev

    Article  PubMed  CAS  Google Scholar 

  4. Lou DY, Dominquez I, Toselli P, Landesman-Bollaq E, O’Brien C, Seldin DC (2008) The alpha catalytic subunit of protein kinase CK2 is required for mouse embryonic development. Mol Cell Biol 28:131–139. doi:10.1128/MCB.01119-07

    Article  PubMed  CAS  Google Scholar 

  5. Xu X, Toselli PA, Russell LD, Seldin DC (1999) Globozoospermia in mice lacking the casein kinase II alpha’ catalytic subunit. Nat Genet 23:118–121. doi:10.1038/12729

    Article  PubMed  CAS  Google Scholar 

  6. Buchou T, Vernet M, Blond O, Jensen HH, Pointu H, Olsen BB et al (2003) Disruption of the regulatory beta subunit of protein kinase CK2 in mice leads to a cell-autonomous defect and early embryonic lethality. Mol Cell Biol 23:908–915. doi:10.1128/MCB.23.3.908-915.2003

    Article  PubMed  CAS  Google Scholar 

  7. Hanna DE, Rethinaswamy A, Glover CV (1995) Casein kinase II is required for cell cycle progression during G1 and G2/M in S. cerevisiae. J Biol Chem 270:25905–25914. doi:10.1074/jbc.270.43.25905

    Article  PubMed  CAS  Google Scholar 

  8. Sayed M, Pelech S, Wong C, Marotta A, Salh B (2001) Protein kinase CK2 is involved in G2 arrest and apoptosis following spindle damage in epithelial cells. Oncogene 20:6994–7005. doi:10.1038/sj.onc.1204894

    Article  PubMed  CAS  Google Scholar 

  9. Yamane K, Kinsella TJ (2005) CK2 inhibits apoptosis and changes its cellular localization following ionizing radiation. Cancer Res 65:4362–4367. doi:10.1158/0008-5472.CAN-04-3941

    Article  PubMed  CAS  Google Scholar 

  10. Li D, Dobrowolska G, Aicher LD, Chen M, Wright JH, Drueckes P et al (1999) Expression of the casein kinase CK2 subunits in CHO and 3T3L1 cells provide information on the role of the enzyme in cell proliferation and the cell cycle. J Biol Chem 274:32988–32996. doi:10.1074/jbc.274.46.32988

    Article  PubMed  CAS  Google Scholar 

  11. Teitz T, Eli D, Penner M, Bakhanashvili M, Naiman T, Timme TL et al (1990) Expression of the cDNA for the beta subunit of human casein kinase II confers partial UV resistance on xeroderma pigmentosum cells. Mutat Res 236:85–97

    PubMed  CAS  Google Scholar 

  12. Olsten MEK, Litchfield DW (2004) Order or chaos? An evaluation of the regulation of protein kinase CK2. Biochem Cell Biol 82:681–693. doi:10.1139/o04-116

    Article  PubMed  CAS  Google Scholar 

  13. Litchfield DW, Dobrowolska G, Krebs EG (1994) Regulation of casein kinase II by growth factors: a re-evaluation. Cell Mol Biol Res 4:373–381

    Google Scholar 

  14. Homma MK, Li D, Krebs EG, Homma Y (2002) Association and regulation of casein kinase 2 activity by adenomatous polyposis coli protein. Proc Natl Acad Sci U S A 99:5959–5964. doi:10.1073/pnas.092143199

    Article  PubMed  CAS  Google Scholar 

  15. Homma MK, Wada I, Suzuki T, Yamaki J, Krebs EG, Homma Y (2005) CK2 phosphorylation of eukaryotic translation initiation factor 5 potentiates cell cycle progression. Proc Natl Acad Sci U S A 102:15688–15693. doi:10.1073/pnas.0506791102

    Article  PubMed  CAS  Google Scholar 

  16. Das S, Maitra U (2001) Functional significance and mechanism of eIF5-promoted GTP hydrolysis in eukaryotic translation initiation. Prog Nucleic Acid Res Mol Biol 70:207–231. doi:10.1016/S0079-6603(01)70018-9

    Article  PubMed  CAS  Google Scholar 

  17. Wang H, Yu S, Davis AT, Ahmed K (2003) Cell cycle dependent regulation of protein kinase CK2 signaling to the nuclear matrix. J Cell Biochem 88:812–822. doi:10.1002/jcb.10438

    Article  PubMed  CAS  Google Scholar 

  18. Filhol O, Nueda A, Martel V, Gerber-Scokaert D, Benitez MJ, Souchier C et al (2003) Live-cell fluorescence imaging reveals the dynamics of protein kinase CK2 individual subunits. Mol Cell Biol 23:957–987. doi:10.1128/MCB.23.3.975-987.2003

    Article  Google Scholar 

  19. Barz T, Ackermann K, Dubois G, Eils R, Pyerin W (2003) Genome-wide expression screens indicate a global role for protein kinase CK2 in chromatin remodeling. J Cell Sci 116:1563–1577. doi:10.1242/jcs.00352

    Article  PubMed  CAS  Google Scholar 

  20. Hase ME, Yalamanchili P, Visa N (2006) The Drosophila heterogenous nuclear ribonucleoprotein M protein, HRP59, regulates alternative splicing and controls the production of its own mRNA. J Biol Chem 281:39135–39141. doi:10.1074/jbc.M604235200

    Article  PubMed  CAS  Google Scholar 

  21. Montagnoli A, Valsasina B, Brotherton D, Troiani S, Rainoldi S, Tenca P et al (2006) Identification of Mcm2 phosphorylation sites by S-phase-regulating kinases. J Biol Chem 281:10281–10290. doi:10.1074/jbc.M512921200

    Article  PubMed  CAS  Google Scholar 

  22. Lemmens L, Urbach S, Prudent R, Cochet C, Baldacci G, Hughes P (2008) Phosphorylation of the C subunit (p66) of human DNA polymerase delta. BBRC 367:264–270

    PubMed  CAS  Google Scholar 

  23. Poon RY (2007) Mitotic phosphorylation: breaking the balance of power by a tactical retreat. Biochem J 403:e5–e7. doi:10.1042/BJ20070290

    Article  PubMed  CAS  Google Scholar 

  24. Cheung W, Turner FB, Krishnamoorthy T, Wolner B, Ahn S-H, Foley M, Dorsey JA, Peterson CL, Berger SL, Allis CD (2005) Phosphorylation of histone H4 serine 1 during DNA damage requires CKII in S. cerevisiae. Curr Biol 15:656–660. doi:10.1016/j.cub.2005.02.049

    Article  PubMed  CAS  Google Scholar 

  25. Panova TB, Panov KI, Russell J, Zomerdijk JCBM (2006) Casein kinase 2 associates with initiation-competent RNA polymerase I and has multiple roles in ribosomal DNA transcription. Mol Cell Biol 26:5957–5968. doi:10.1128/MCB.00673-06

    Article  PubMed  CAS  Google Scholar 

  26. Assrir N, Filhol O, Galisson F, Lipinski M (2007) HIRIP3 is a nuclear phosphoprotein interacting with and phosphorylated by the serine-threonin kinase CK2. Biol Chem 388:391–398. doi:10.1515/BC.2007.045

    Article  PubMed  CAS  Google Scholar 

  27. Vera J, Estanyol JM, Canela N, Llorens F, Agell N, Itarte E et al (2007) Proteomic analysis of SET-binding proteins. Proteomics 7:578–587. doi:10.1002/pmic.200600458

    Article  PubMed  CAS  Google Scholar 

  28. Mailand N (2007) Human Xip1(C2orf13) is a novel regulator of cellular response to DNA strand breaks. J Biol Chem 282:19638–19643

    Article  PubMed  Google Scholar 

  29. Pi J, Bai Y, Reece JM, Williams J, Liu D, Freeman ML et al (2007) Molecular mechanism of human Nrf2 activation and degradation: role of sequential phosphorylation by protein kinase CK2. Free Radic Biol Med 42:1797–1806. doi:10.1016/j.freeradbiomed.2007.03.001

    Article  PubMed  CAS  Google Scholar 

  30. Takemoto A, Kimura K, Yanagisawa J, Yokoyama S, Hanaoka F (2006) Negative regulation of condensin I by CK2-mediated phosphorylation. EMBO J 25:5339–5348. doi:10.1038/sj.emboj.7601394

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We acknowledge Dr. Ahmed K for the critical reading of the manuscript; Drs. D. Li and E.G. Krebs for many helpful discussions. This work was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan.

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  1. Department of Biomolecular Science, Fukushima Medical University School of Medicine, 1-Hikari-gaoka, Fukushima, 960-1295, Japan

    Miwako Kato Homma & Yoshimi Homma

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  1. Miwako Kato Homma
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  2. Yoshimi Homma
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Correspondence to Miwako Kato Homma.

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Homma, M.K., Homma, Y. Cell cycle and activation of CK2. Mol Cell Biochem 316, 49–55 (2008). https://doi.org/10.1007/s11010-008-9823-4

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  • DOI: https://doi.org/10.1007/s11010-008-9823-4

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