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Molecular and Cellular Biochemistry

, Volume 274, Issue 1–2, pp 163–170 | Cite as

A global view of CK2 function and regulation

  • Allison Poole
  • Tim Poore
  • Sricharan Bandhakavi
  • Richard O. McCann
  • David E. Hanna
  • Claiborne V. C. Glover
Article

Abstract

The wealth of biochemical, molecular, genetic, genomic, and bioinformatic resources available in S. cerevisiae make it an excellent system to explore the global role of CK2 in a model organism. Traditional biochemical and genetic studies have revealed that CK2 is required for cell viability, cell cycle progression, cell polarity, ion homeostasis, and other functions, and have identified a number of potential physiological substrates of the enzyme. Data mining of available bioinformatic resources indicates that (1) there are likely to be hundreds of CK2 targets in this organism, (2) the majority of predicted CK2 substrates are involved in various aspects of global gene expression, (3) CK2 is present in several nuclear protein complexes predicted to have a role in chromatin structure and remodeling, transcription, or RNA metabolism, and (4) CK2 is localized predominantly in the nucleus. These bioinformatic results suggest that the observed phenotypic consequences of CK2 depletion may lie downstream of primary defects in chromatin organization and/or global gene expression. Further progress in defining the physiological role of CK2 will almost certainly require a better understanding of the mechanism of regulation of the enzyme. Beginning with the crystal structure of the human CK2 holoenzyme, we present a molecular model of filamentous CK2 that is consistent with earlier proposals that filamentous CK2 represents an inactive form of the enzyme. The potential role of filamentous CK2 in regulation in vivo is discussed.

Keywords

bioinformatics filamentous CK2 genomics and proteomics molecular modeling protein kinase CK2 

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References

  1. 1.
    Meggio F, Pinna LA: One-thousand-and-one substrates of protein kinase CK2? FASEB J 17: 349–368, 2003PubMedGoogle Scholar
  2. 2.
    Litchfield DW: Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem J 369: 1–15, 2003PubMedGoogle Scholar
  3. 3.
    Glover CV: A filamentous form of Drosophila casein kinase II. J Biol Chem 261: 14349–14354, 1986PubMedGoogle Scholar
  4. 4.
    Valero E, De Bonis S, Filhol O, Wade RH, Langowski J, Chambaz EM, Cochet C: Quaternary structure of casein kinase 2. Characterization of multiple oligomeric states and relation with its catalytic activity. J Biol Chem 270: 8345–8352, 1995PubMedGoogle Scholar
  5. 5.
    Glover CV, 3rd: On the physiological role of casein kinase II in Saccharomyces cerevisiae. Prog Nucleic Acid Res Mol Biol 59: 95–133, 1998PubMedGoogle Scholar
  6. 6.
    Padmanabha R, Chen-Wu JL, Hanna DE, Glover CV: 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, 1990PubMedGoogle Scholar
  7. 7.
    Hanna DE, Rethinaswamy A, Glover CV: Casein kinase II is required for cell cycle progression during G1 and G2/M in {Saccharomyces cerevisiae}. J Biol Chem 270: 25905–25914, 1995PubMedGoogle Scholar
  8. 8.
    Rethinaswamy A, Birnbaum MJ, Glover CV: Temperature-sensitive mutations of the CKA1 gene reveal a role for casein kinase II in maintenance of cell polarity in {Saccharomyces cerevisiae}. J Biol Chem 273: 5869–5877, 1998PubMedGoogle Scholar
  9. 9.
    Bidwai AP, Reed JC, Glover CV: Cloning and disruption of CKB1, the gene encoding the 38-kDa beta subunit of Saccharomyces cerevisiae casein kinase II (CKII). Deletion of CKII regulatory subunits elicits a salt-sensitive phenotype. J Biol Chem 270: 10395–10404, 1995PubMedGoogle Scholar
  10. 10.
    Toczyski DP, Galgoczy DJ, Hartwell LH: CDC5 and CKII control adaptation to the yeast DNA damage checkpoint. Cell 90: 1097–1106, 1997PubMedGoogle Scholar
  11. 11.
    Bandhakavi S, McCann RO, Hanna DE, Glover CV: Genetic interactions among ZDS1,2, CDC37, and protein kinase CK2 in Saccharomyces cerevisiae. FEBS Lett 554: 295–300, 2003PubMedGoogle Scholar
  12. 12.
    Bandhakavi S, McCann RO, Hanna DE, Glover CV: A positive feedback loop between protein kinase CKII and Cdc37 promotes the activity of multiple protein kinases. J Biol Chem 278: 2829–2836, 2003PubMedGoogle Scholar
  13. 13.
    Cardenas ME, Dang Q, Glover CV, Gasser SM: Casein kinase II phosphorylates the eukaryote-specific C-terminal domain of topoisomerase II in~vivo. EMBO J 11: 1785–1796, 1992PubMedGoogle Scholar
  14. 14.
    Feng L, Yoon H, Donahue TF: Casein kinase II mediates multiple phosphorylation of Saccharomyces cerevisiae eIF-2 alpha (encoded by SUI2), which is required for optimal eIF-2 function in S. cerevisiae. Mol Cell Biol 14: 5139–5153, 1994PubMedGoogle Scholar
  15. 15.
    Ghavidel A, Schultz MC: TATA binding protein-associated CK2 transduces DNA damage signals to the RNA polymerase III transcriptional machinery. Cell 106: 575–584, 2001PubMedGoogle Scholar
  16. 16.
    Miyata Y, Nishida E: CK2 controls multiple protein kinases by phosphorylating a kinase-targeting molecular chaperone, Cdc37. Mol Cell Biol 24: 4065–4074, 2004PubMedGoogle Scholar
  17. 17.
    Bader GD, Heilbut A, Andrews B, Tyers M, Hughes T, Boone C: Functional genomics and proteomics: charting a multidimensional map of the yeast cell. Trends Cell Biol 13: 344–356, 2003PubMedGoogle Scholar
  18. 18.
    Hulo N, Sigrist CJ, Le Saux V, Langendijk-Genevaux PS, Bordoli L, Gattiker A, De Castro E, Bucher P, Bairoch A: Recent improvements to the PROSITE database. Nucleic Acids Res 32: D134–137, 2004PubMedGoogle Scholar
  19. 19.
    Obenauer JC, Cantley LC, Yaffe MB: Scansite 2.0: proteome-wide prediction of cell signaling interactions using short sequence motifs. Nucleic Acids Res 31: 3635–3641, 2003PubMedGoogle Scholar
  20. 20.
    Schwede T, Kopp J, Guex N, Peitsch MC: SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Res 31: 3381–3385, 2003PubMedGoogle Scholar
  21. 21.
    Ficarro SB, McCleland ML, Stukenberg PT, Burke DJ, Ross MM, Shabanowitz J, Hunt DF, White FM: Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat Biotechnol 20: 301–305, 2002PubMedGoogle Scholar
  22. 22.
    Uetz P, Giot L, Cagney G, Mansfield TA, Judson RS, Knight JR, Lockshon D, Narayan V, Srinivasan M, Pochart P, Qureshi-Emili A, Li Y, Godwin B, Conover D, Kalbfleisch T, Vijayadamodar G, Yang M, Johnston M, Fields S, Rothberg JM: A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae. Nature 403: 623–627, 2000PubMedGoogle Scholar
  23. 23.
    Gavin AC, Bosche M, Krause R, Grandi P, Marzioch M, Bauer A, Schultz J, Rick JM, Michon AM, Cruciat CM, Remor M, Hofert C, Schelder M, Brajenovic M, Ruffner H, Merino A, Klein K, Hudak M, Dickson D, Rudi T, Gnau V, Bauch A, Bastuck S, Huhse B, Leutwein C, Heurtier MA, Copley RR, Edelmann A, Querfurth E, Rybin V, Drewes G, Raida M, Bouwmeester T, Bork P, Seraphin B, Kuster B, Neubauer G, Superti-Furga G: Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415: 141–147, 2002PubMedGoogle Scholar
  24. 24.
    Hazbun TR, Malmstrom L, Anderson S, Graczyk BJ, Fox B, Riffle M, Sundin BA, Aranda JD, McDonald WH, Chiu CH, Snydsman BE, Bradley P, Muller EG, Fields S, Baker D, Yates JR, 3rd, Davis TN: Assigning function to yeast proteins by integration of technologies. Mol Cell 12: 1353–1365, 2003PubMedGoogle Scholar
  25. 25.
    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, 2002PubMedGoogle Scholar
  26. 26.
    Hughes TR, Marton MJ, Jones AR, Roberts CJ, Stoughton R, Armour CD, Bennett HA, Coffey E, Dai H, He YD, Kidd MJ, King AM, Meyer MR, Slade D, Lum PY, Stepaniants SB, Shoemaker DD, Gachotte D, Chakraburtty K, Simon J, Bard M, Friend SH: Functional discovery via a compendium of expression profiles. Cell 102: 109–126, 2000PubMedGoogle Scholar
  27. 27.
    Peng WT, Robinson MD, Mnaimneh S, Krogan NJ, Cagney G, Morris Q, Davierwala AP, Grigull J, Yang X, Zhang W, Mitsakakis N, Ryan OW, Datta N, Jojic V, Pal C, Canadien V, Richards D, Beattie B, Wu LF, Altschuler SJ, Roweis S, Frey BJ, Emili A, Greenblatt JF, Hughes TR: A panoramic view of yeast noncoding RNA processing. Cell 113: 919–933, 2003PubMedGoogle Scholar
  28. 28.
    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, 2003PubMedGoogle Scholar
  29. 29.
    Tong AH, Lesage G, Bader GD, Ding H, Xu H, Xin X, Young J, Berriz GF, Brost RL, Chang M, Chen Y, Cheng X, Chua G, Friesen H, Goldberg DS, Haynes J, Humphries C, He G, Hussein S, Ke L, Krogan N, Li Z, Levinson JN, Lu H, Menard P, Munyana C, Parsons AB, Ryan O, Tonikian R, Roberts T, Sdicu AM, Shapiro J, Sheikh B, Suter B, Wong SL, Zhang LV, Zhu H, Burd CG, Munro S, Sander C, Rine J, Greenblatt J, Peter M, Bretscher A, Bell G, Roth FP, Brown GW, Andrews B, Bussey H, Boone C: Global mapping of the yeast genetic interaction network. Science 303: 808–813, 2004PubMedGoogle Scholar
  30. 30.
    Huh WK, Falvo JV, Gerke LC, Carroll AS, Howson RW, Weissman JS, O’Shea EK: Global analysis of protein localization in budding yeast. Nature 425: 686–691, 2003PubMedGoogle Scholar
  31. 31.
    Krek W, Maridor G, Nigg EA: Casein kinase II is a predominantly nuclear enzyme. J Cell Biol 116: 43–55, 1992PubMedGoogle Scholar
  32. 32.
    Holstege FC, Jennings EG, Wyrick JJ, Lee TI, Hengartner CJ, Green MR, Golub TR, Lander ES, Young RA: Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95: 717–728, 1998PubMedGoogle Scholar
  33. 33.
    Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O’Shea EK, Weissman JS: Global analysis of protein expression in yeast. Nature 425: 737–741, 2003PubMedGoogle Scholar
  34. 34.
    Pinna LA: Protein kinase CK2: a challenge to canons. J Cell Sci 115: 3873–3878, 2002PubMedGoogle Scholar
  35. 35.
    Faust M, Montenarh M: Subcellular localization of protein kinase CK2. A key to its function? Cell Tissue Res 301: 329–340, 2000Google Scholar
  36. 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, 2001PubMedGoogle Scholar
  37. 37.
    Pagano MA, Sarno S, Poletto G, Cozza G, Pinna LA, Meggio F: Autophosphorylation at the regulatory β subunit reflects the supramolecular organization of protein kinase CK2. Mol Cell Biochem 274: 23–29, 2005Google Scholar
  38. 38.
    Rekha N, Srinivasan N: Structural basis of regulation and substrate specificity of protein kinase CK2 deduced from the modeling of protein-protein interactions. BMC Struct Biol 3: 4, 2003PubMedGoogle Scholar
  39. 39.
    Chantalat L, Leroy D, Filhol O, Nueda A, Benitez MJ, Chambaz EM, Cochet C, Dideberg O: Crystal structure of the human protein kinase CK2 regulatory subunit reveals its zinc finger-mediated dimerization. EMBO J 18: 2930–2940, 1999PubMedGoogle Scholar
  40. 40.
    Lee I, Date SV, Adai AT, Marcotte EM: A probabilistic functional network of yeast genes. Science 306: 1555–1558, 2004PubMedGoogle Scholar
  41. 41.
    Theis-Febvre N, Martel V, Laudet B, Souchier C, Grunwald D, Cochet C, Filhol O: Highlighting protein kinase CK2 movement in living cells. Mol Cell Biochem 274: 15–22, 2005Google Scholar
  42. 42.
    Tenney KA, Glover CV: Transcriptional regulation of the S. cerevisiae ENA1 gene by casein kinase II. Mol Cell Biochem 191: 161–167, 1999PubMedGoogle Scholar
  43. 43.
    de Nadal E, Calero F, Ramos J, Arino J: Biochemical and genetic analyses of the role of yeast casein kinase 2 in salt tolerance. J Bacteriol 181: 6456–6462, 1999PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Allison Poole
    • 1
  • Tim Poore
    • 1
  • Sricharan Bandhakavi
    • 1
    • 2
  • Richard O. McCann
    • 1
    • 3
  • David E. Hanna
    • 1
  • Claiborne V. C. Glover
    • 1
    • 4
  1. 1.Department of Biochemistry and Molecular BiologyThe University of GeorgiaAthensUSA
  2. 2.Department of Biochemistry, Molecular Biology, and BiophysicsUniversity of MinnesotaMinneapolisUSA
  3. 3.Department of Molecular and Cellular BiochemistryUniversity of KentuckyLexingtonUSA
  4. 4.Department of Biochemistry and Molecular Biology, Life Sciences BuildingThe University of GeorgiaAthensUSA

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