Skip to main content
SpringerLink
Log in

Protein kinase CK2 in gene control at cell cycle entry

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Protein kinase CK2 has diverse links to gene control and cell cycle. Comparative genome-wide expression profiling of CK2 mutants of the budding yeast Saccharomyces cerevisiae at cell cycle entry has revealed that a significant proportion of cell-cycle genes are affected by CK2. Here, we examine how CK2 realizes this effect. We show that the CK2 action may be directed to gene promoters causing genes with promoter homologies to respond comparably to CK2 perturbation. Examples are metabolic pathway and nutrition supply genes such as the PHO and MET regulon genes, responsible for phosphate maintenance and methionine biosynthesis, respectively. CK2 perturbation affects both regulons permanently and both via repression of a central transcription factor, but with different mechanisms: In the PHO regulon, the gene encoding the central transcription factor Pho4 is repressed and, in addition, Pho4 and/or the cyclin-dependent kinase of the regulon’s control complex may be affected by CK2 phosphorylation. In the MET regulon, the repression of the central transcription factor Met4 occurs not by expression inhibition, but rather by availability tuning via a CK2-mediated phosphorylation of a degradation complex. On the other hand, the CK2 action may be directed to the chromatin regulon, thus affecting globally the expression of genes, i.e., the CK2 perturbation results either in comparable responses of genes which have no promoter homologies or in deviating responses despite promoter homologies. The effect is rather transient and concerns aside various cell cycle control genes a notable number of genes encoding chromatin remodeling and modification proteins with functions in chromatin assembly and (anti-)silencing as well as in histone (de-)acetylation, and frequently are also substrates of CK2, suggesting additional tuning at protein level. In line with these findings, we observe in human cells sequence-independent but cell-cycle-dependent CK2 associations with promoters of cell-cycle-regulated genes at periods of extensive gene expression alterations, including cell cycle entry. Our observations are compatible with the idea that the gene control by CK2 is achieved via different mechanisms and at different levels of organization and includes a global role in transcription-related chromatin remodelling and modification.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Pinna LA: Protein kinase CK2: A challenge to canons. J Cell Sci 115: 3873–3878, 2002

    PubMed  Google Scholar 

  2. Pyerin W, Ackermann K, Lorenz P: Casein kinases. In: F. Marks (ed). Protein Phosphorylation. Verlag Chemie, Weinheim, 1996, pp 117–174

    Google Scholar 

  3. Gavin AC, Bosche M, Krause R, Grandi P, Marzioch M, Bauer A, Schultz J, Rick JM, Michon AM, et al.: Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415: 141–147, 2002

    PubMed  Google Scholar 

  4. Ho Y, Gruhler A, Heilbut A, Bader GD, Moore L, Adams SL, Millar A, Taylor P, Bennett K, et~al.: Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415: 180–183

  5. Ahmed K, Gerber DA, Cochet C: Joining the cell survival squad: An emerging role for protein kinase CK2. Trends Cell Biol 12: 226–230, 2002

    PubMed  Google Scholar 

  6. Gauthier-Rouvière C, Basset M, Blanchard JM, Cavadore JC, Fernandez A, Lamb NJC: Casein kinase II induces c-fos expression via the serum response element pathway and p67SRF phosphorylation in living fibroblasts. EMBO J 10: 2921–2930, 1991

    PubMed  Google Scholar 

  7. Pepperkok R, Lorenz P, Ansorge W, Pyerin W: Casein kinase II is required for transition of G0/G1, early G1, and G1/S phases of the cell cycle. J Biol Chem 269: 6986–6991, 1994

    PubMed  Google Scholar 

  8. Pepperkok R, Herr S, Lorenz P, Pyerin W, Ansorge W: System for quantitation of gene expression in single cells by computerized microimaging: Application to c-fos expression after microinjection of anti-casein kinase II antibody. Exp Cell Res 204: 278–285, 1993

    PubMed  Google Scholar 

  9. Iyer VR, Eisen MB, Ross DT, Schuler G, Moore T, Lee JC, Trent JM, Staudt LM, Hudson J Jr, et~al.: The transcriptional program in the response of human fibroblasts to serum. Science 283: 83–87, 1999

    PubMed  Google Scholar 

  10. Glover CVC: On the physiological role of casein kinase II in Saccharomyces cerevisiae. Prog Nucleic Acid Res 59: 95–133, 1998

    PubMed  Google Scholar 

  11. Litchfield DW, Lüscher B: Casein kinase II in signal transduction and cell cycle regulation. Mol Cell Biochem 127/128: 187–199, 1993

    Google Scholar 

  12. Pyerin W, Ackermann K: The genes encoding human protein kinase CK2 and their functional links. Progr Nucl Acid Res Mol Biol 74: 239–273, 2003

    Google Scholar 

  13. Lorenz P, Pepperkok R, Ansorge W, Pyerin W: Cell biological studies with monoclonal and polyclonal antibodies against human casein kinase II subunit beta demonstrate participation of the kinase in mitogenic signaling. J Biol Chem 268: 2733–2739, 1993

    PubMed  Google Scholar 

  14. Lorenz P, Ackermann K, Simoes-Wuest P, Pyerin W: Serum-stimulated cell cycle entry of fibroblasts requires undisturbed phosphorylation and non-phosphorylation interactions of the catalytic subunits of protein kinase CK2. FEBS Lett 448: 283–288, 1999

    PubMed  Google Scholar 

  15. Ahmed K: Nuclear matrix and protein kinase CK2 signaling. Crit Rev Eukaryot Gene Expr 9: 329–336, 1999

    PubMed  Google Scholar 

  16. Pepperkok R, Lorenz P, Jakobi R, Ansorge W, Pyerin W: Cell growth stimulation by EGF: inhibition through antisense-oligodeoxynucleotides demonstrates important role of casein kinase II. Exp Cell Res 197: 245–253, 1991

    PubMed  Google Scholar 

  17. Ole-MoiYoi OK: Casein Kinase II in Theileriosis. Science 267: 834–836, 1995

    PubMed  Google Scholar 

  18. Seldin DC, Leder P: Casein kinase IIα transgene-induced murine lymphoma: Relation to theileriosis in cattle. Science 267: 894–897, 1995

    PubMed  Google Scholar 

  19. Landesmann-Bollag E, Romieu-Mourez R, Song DH, Sonenshein GE, Cardiff RD, Seldin DC: Protein kinase CK2 in mammary gland tumorigenesis. Oncogene 20: 3247–3257, 2001

    Google Scholar 

  20. Rifkin R, Channavajhala PL, Kiefer HLB, Carmack AJ, Landesmann-Bollag E, Beaudette BC, Jersky B, Salant DJ, Ju ST, Marshak-Rothstein A, Seldin DC: Acceleration of lpr lymphoproliferative and autoimmune disease by transgenic protein kinase ck2α. J Immunol 161: 5164–5170, 1998

    PubMed  Google Scholar 

  21. Blanquet R: Casein kinase 2 as a potentially important enzyme in the nervous system. Progr Neurobiol 60: 211–246, 2000

    PubMed  Google Scholar 

  22. Ackermann K, Waxmann A, Glover CVC, Pyerin W: Genes targeted by CK2: A genome-wide expression array analysis in yeast. Mol Cell Biochem 227: 59–66, 2001

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  24. Barz T, Ackermann K, Pyerin, W: Perturbation of protein kinase CK2 uncouples executive part of phosphate maintenance pathway from cyclin-CDK control. FEBS Lett 537: 210–214, 2003

    PubMed  Google Scholar 

  25. Bidwai AP, Reed JC, Glover CVC: Cloning and disruption of CKB1, the gene encoding the 38-kDa ß subunit of Saccharomyces cerevisiae casein kinase II (CKII). J Biol Chem 270: 10395–10414, 1995

    PubMed  Google Scholar 

  26. Chen-Wu JL, Padmanabha R, Glover CVC: Isolation, sequencing, and disruption of the CKA1 gene encoding the alpha subunit of yeast casein kinase II. Mol Cell Biol 8: 4981–4990, 1988

    PubMed  Google Scholar 

  27. Padmanabha R, Chen-Wu JL, Hanna DE, Glover CVC: Isolation, sequencing, and disruption of the yeast CKA2 gene: Casein kinase II is essential for viability in Saccharomyces cerevisiae. Mol Cell Biol 10: 4089–4099, 1990

    PubMed  Google Scholar 

  28. Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB, Brown PO, Botstein D, Futcher B.: Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9: 3273–3297, 1998

    PubMed  Google Scholar 

  29. Krehan A, Lorenz P, Plana-Coll M, Pyerin W: Interaction sites between catalytic and regulatory subunits in human protein kinase CK2 holoenzymes as indicated by chemical cross-linking and immunological investigations. Biochemistry 35: 4966–4975, 1996

    PubMed  Google Scholar 

  30. Cho JR, Campbell MJ, Winzeler EA, Steinmetz L, Conway A, Wodicka L, Wolfsberg TL, Gabrielian AT, Landsman D, et~al.: A genome-wide transcriptional analysis of the mitotic cell cycle. Mol Cell 2: 65–73, 1998

    PubMed  Google Scholar 

  31. Lenburg ME, O’Shea EK: Signaling phosphate starvation. TIBS 21: 383–387, 1996

    PubMed  Google Scholar 

  32. Ogawa N, DeRisi J, Brown PO: New components of a system for phosphate accumulation and polyphosphate metabolism in Saccharomyces cerevisiae revealed by genomic expression analysis. Mol Biol Cell 11: 4309–4321, 2000

    PubMed  Google Scholar 

  33. Wykoff DD, O’Shea EK: Phosphate transport and sensing in Saccharomyces cerevisiae. Genetics 159: 1491–1499, 2001

    PubMed  Google Scholar 

  34. Jeffery DA, Springer M; King DS, O’Shea EK: Multi-site phosphorylation of Pho4 by the cyclin-CDK Pho80-Pho85 is semi-processive with site preference. J Mol Biol 306: 997–1010, 2001

    PubMed  Google Scholar 

  35. Moffat J, Huang D, Andrews B: Functions of Pho85 cyclin-dependent kinases in budding yeast. Progr Cell Cycle Res 4: 97–106, 2000

    Google Scholar 

  36. Niefind K, Guerra B, Ermakowa I, Issinger OG: Crystal structure of human protein kinase CK2: Insights into basic properties of the CK2 holoenzyme. EMBO J 20: 5320–5331, 2001

    PubMed  Google Scholar 

  37. Blaiseau PL, Thomas D: Multiple transcriptional activation complexes tether the yeast activator Met4 to DNA. EMBO J 17: 6327–6336, 1998

    PubMed  Google Scholar 

  38. Patton EE, Peyraud C; Rouillon A, Surdin-Kerjan Y, Tyers M, Thomas D: SCF(Met30)-mediated control of the transcriptional activator Met4 is required for the G1-S transition. EMBO J 19: 1613–1624, 2000

    CAS  PubMed  Google Scholar 

  39. Kuras L; Rouillon A, Lee T, Barbey R, Tyers M, Thomas D: Dual regulation of the Met4 transcription factor by ubiquitin-dependent degradation and inhibition of promoter recruitment. Mol Cell 10: 69–80, 2002

    PubMed  Google Scholar 

  40. Alberts B, Johnson A, Lewis J, Raff M, Roberts, K, Walter P: Molecular biology of the cell. Garland Sci, USA, 2002

  41. Cosma MP: Ordered recruitment: gene-specific mechanism of transcription activation. Mol Cell 10: 227–36, 2002

    PubMed  Google Scholar 

  42. Krude T, Keller C: Chromatin assembly during S-phase: contributions from histone deposition, DNA replication and the cell division cycle. Cell Mol Life Sci 58: 665–672, 2001

    PubMed  Google Scholar 

  43. Tsukiyama T: The in vivo functions of ATP-dependent chromatin-remodeling factors. Nat Rev Mol Cell Biol 3: 422–429, 2002

    PubMed  Google Scholar 

  44. Sarmento OF, Digilio LC, Wang Y, Perlin J, Herr JC, Allis CD, Coonrod SA: Dynamic alterations of specific histone modifications during early murine development. J Cell Sci 117: 4449–4459, 2004

    PubMed  Google Scholar 

  45. Reyes JC, Barra J, Muchardt C, Camus A, Babinet C, Yaniv M: Altered control of cellular proliferation in the absence of mammalian brahma (SNF2alpha). EMBO J 17: 6779–6791, 1998

    Google Scholar 

  46. Krogan NJ, Kim M, Ahn SH, Zhong G, Kobor MS, Cagney G, Emili A, Shilatifard A, Buratowski S, Greenblatt JF: RNA polymerase II elongation factors of Saccharomyces cerevisiae: A targeted proteomics approach. Mol Cell Biol 22, 6979–6992, 2002

    PubMed  Google Scholar 

  47. Sawa C, Nedea E, Krogan N, Wada T, Handa H, Greenblatt J, Buratowski S: Bromodomain factor 1 (Bdf1) is phosphorylated by protein kinase CK2. Mol Cell Biol 24: 4734–4742, 2004

    PubMed  Google Scholar 

  48. Tsai SC, Seto E: Regulation of histone deacetylase 2 by protein kinase CK2. J Biol Chem 277: 31826–31833, 2002

    PubMed  Google Scholar 

  49. Kappes F, Damoc C, Knippers R, Przybylski M, Pinna LA, Gruss C: Phosphorylation by protein kinase CK2. Mol Cell Biol 24: 6011–6020, 2004

    PubMed  Google Scholar 

  50. Krohn NM, Yanagisawa S, Grasser KD: Specificity of the stimulatory interaction between chromosomal HMGB proteins and the transcription factor Dof2 and its negative regulation by protein kinase CK2-mediated phosphorylation. J Biol Chem 277: 32438–32444, 2002

    PubMed  Google Scholar 

  51. Loizou JI, El-Khamisy SF, Zlatanou A, Moore DJ, Chan DW, Qin J, Sarno S, Meggio F, Pinna LA, Caldecott, KW: The protein kinase CK2 facilitates repair of chromosomal DNA single strand breaks. Cell 117: 17–28, 2004

    PubMed  Google Scholar 

  52. Zhao T, Heyduk T, Eissenberg JC: Phosphorylation site mutations in heterochromatin protein 1 (HP1) reduce or eliminate silencing activity. J Biol Chem 276: 9512–9518, 2001

    PubMed  Google Scholar 

  53. Wisniewski JR, Szewczuk Z, Petry I, Schwanbeck R, Renner U: Constitutive phosphorylation of the acidic tails of the high mobility group 1 proteins by casein kinase II alters their conformation, stability, and DNA binding specificity. J Biol Chem 274: 20116–20122, 1999

    PubMed  Google Scholar 

  54. Stemmer C, Schwander A, Bauw G, Fojan P, Grasser KD: Protein kinase CK2 differentially phosphorylates maize chromosomal high mobility group B (HMGB) proteins modulating their stability and DANN interactions. J Biol Chem 277: 1092–1098, 2002

    PubMed  Google Scholar 

  55. Guo C, Davis AT, Ahmed K: Dynamics of protein kinase CK2 association with nucleosomes in relation to transcriptional activity. J Biol Chem 273: 13675–13680, 1998

    PubMed  Google Scholar 

  56. Guo C, Davis AT, Yu S, Tawfic S, Ahmed K: Role of protein kinase CK2 in phosphorylation of nucleosomal proteins in relation to transcriptional activity. Mol Cell Biochem 191: 135–142, 1999

    PubMed  Google Scholar 

  57. Li M, Strand D, Krehan A, Pyerin W, Heid H, Neumann B, Mechler M: Casein kinase 2 binds and phosphorylates the nucleosome assembly protein-1 (NAP1) in Drosophila melanogaster. J Mol Biol 293: 1067–1084, 1999

    PubMed  Google Scholar 

  58. Rodriguez P, Pelletier J, Price GB, Zannis-Hadjopoulos M: NAP-2: Histone chaperone function and phosphorylation state through the cell cycle. J Mol Biol 298: 225–238, 2000

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biochemische Zellphysiologie (A135), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Walter Pyerin, Thomas Barz & Karin Ackermann

Authors
  1. Walter Pyerin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Barz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karin Ackermann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Walter Pyerin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pyerin, W., Barz, T. & Ackermann, K. Protein kinase CK2 in gene control at cell cycle entry. Mol Cell Biochem 274, 189–200 (2005). https://doi.org/10.1007/s11010-005-2951-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-005-2951-1

Keywords

Search

Navigation