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Protein kinase CK2 interacts with a multi-protein binding domain of p53

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Abstract

p53 is one of the most powerful negative regulators of growth. To manage this in an efficient way it has to interact with a set of different cellular proteins. Most contacts with the cellular environment occur in the N- or the C-terminal domain of the protein. Since we previously found that p53 binds to the regulatory β-subunit of CK2 we now analyzed N- and C-terminal domains of p53 separately for the binding of protein kinase CK2, an enzyme which seems to have a certain importance for proliferation processes. With different overlay assays we could map the binding domain of protein kinase CK2 to a sequence between amino acids 325-344, a region which coincides with the interaction domain of some other p53 binding proteins. We also found that the regulatory β-subunit of protein kinase CK2 binds independent of the catalytic α-subunit to this C-terminal domain of p53.

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References

  1. Götz C, Montenarh M: p53: DNA-damage, DNA repair and apoptosis. Rev Physiol Biochem Pharmacol 127: 65–95, 1995

    Google Scholar 

  2. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B: WAFI, a potential mediator of p53 tumor suppression. Cell 75: 817–825, 1993

    PubMed  Google Scholar 

  3. Okamoto K, Beach D: Cyclin G is a transcriptional target of the p53 tumor suppressor protein. EMBO J 13: 4816–4822, 1994

    PubMed  Google Scholar 

  4. Carrier F, Smith ML, Bae 1, Kilpatrick KE, Lansing TJ, Chen C-Y, Engelstein M, Friend SH, Henner WD, Gilmer TM, Kastan MB, Fornace AJ: Characterization of human Gadd45, a p53-regulated protein. J Biol Chem 269: 32672–32677, 1994

    PubMed  Google Scholar 

  5. Smith ML, Chen I-T, Zhan Q, Bae I, Chen C-Y, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ: Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science 266: 1376–1380, 1994

    PubMed  Google Scholar 

  6. Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B, Reed JC: Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 9: 1799–1805, 1994

    PubMed  Google Scholar 

  7. Bertherat J: Insulin-like growth factor binding protein 3 (IGFBP-3): A novel target of the tumor suppressor p53 inhibiting cell growth. Eur J Endocrinol 134: 426–427, 1996

    PubMed  Google Scholar 

  8. Leng P, Brown DR, Shivakumar CV, Deb S, Deb SP: N-terminal 130 amino acids of MDM2 are sufficient to inhibit p53-mediated transcriptional activation. Oncogene 10: 1275–1282, 1995

    PubMed  Google Scholar 

  9. Wu X, Bayle JH, Olson D, Levine AJ: The p53-mdm-2 autoregulatory feedback loop. Genes Dev 7: 1126–1132, 1993

    PubMed  Google Scholar 

  10. Soussi T, May P: Structural aspects of the p53 protein in relation to gene evolution: A second look. J Mol Biol 260: 623–637, 1996

    PubMed  Google Scholar 

  11. Chen J, Marechal V, Levine AJ: Mapping of the p53 and mdm-2 interaction domains. Mol Cell Biol 13: 4107–4114, 1993

    PubMed  Google Scholar 

  12. Wagner P: p53 forms tight complexes with tmsl of fission yeast. Int J Oncol 4: 987–992, 1994

    Google Scholar 

  13. Appel K, Schneider E, Wagner P, Höog J-O, Karlsson C, Montenarh M: A new 42 KDa protein binding to the growth suppressor protein p53. Int J Oncol 5: 667–673, 1994

    Google Scholar 

  14. Delphin C, Huang KP, Scotto C, Chapel A, Vincon M, Chambaz E, Garin J, Baudier J: The in vitro phosphorylation of p53 by calcium-dependent protein kinase C-Characterization of a protein-kinase-C-binding site on p53. Eur J Biochem 245: 684–692, 1997

    PubMed  Google Scholar 

  15. Kraiss S, Barnekow A, Montenarh M: Protein kinase activity associated with immunopurified p53 protein. Oncogene 5: 845–855, 1990

    PubMed  Google Scholar 

  16. Herrmann CPE, Kraiss S, Montenarh M: Association of casein kinase II with immunopurified p53. Oncogene 6: 877–884, 1991

    PubMed  Google Scholar 

  17. Allende JE, Allende CC: Protein kinase CK2: An enzyme with multiple substrates and puzzling regulation. FASEB J 9: 313–323, 1995

    PubMed  Google Scholar 

  18. 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 

  19. Prowald K, Fischer H, Issinger OG: Enhanced casein kinase II activity in human tumour cell cultures. FEBS Letters 176: 479–483, 1984

    PubMed  Google Scholar 

  20. Münstermann U, Fritz G, Seitz G, Yiping L, Schneider HR, Issinger O-G: Casein kinase II is elevated in human tumours and rapidly proliferating non-neoplastic tissue. Eur J Biochem 189: 251–257, 1990

    PubMed  Google Scholar 

  21. Appel K, Wagner P, Boldyreff B, Issinger O-G, Montenarh M: Mapping of the interaction sites of the growth suppressor protein p53 with the regulatory β-subunit of protein kinase CK2. Oncogene 11: 1971–1978, 1995

    PubMed  Google Scholar 

  22. Miller M, Lubkowski J, Rao JKM, Danishefsky AT, Omichinski JG, Sakaguchi K, Sakamoto H, Appella E, Gronenbom AM, Clore GM: The oligomerization domain of p53: Crystal structure of the trigonal form. FEBS Letters 399: 166–170, 1996

    PubMed  Google Scholar 

  23. Wagner P, Fuchs A, Prowald A, Montenarh M, Nastainczyk W: Precise mapping of the tms1 binding site on p53. FEBS Letters 377: 155–158, 1995

    PubMed  Google Scholar 

  24. Wagner P, Fuchs A, Nastainczyk W, Götz C, Montenarh M: Fine mapping and regulation of the association of p53 and p34 cdc2. Oncogene 16: 105–111, 1998

    PubMed  Google Scholar 

  25. Nevels M, Rubenwolf S, Spruss T, Wolf H, Dobner T: The adenovirus E4orf6 protein can promote E1A/E1 B-induced focus formation by interfering with p53 tumor-suppressor function. Proc Natl Acad Sci USA 94: 1206–1211, 1997

    PubMed  Google Scholar 

  26. Grankowski N, Boldyreff B, Issinger O-G: Isolation and characterization of recombinant human casein kinase II subunits α and β from bacteria. Eur J Biochem 198: 25–30, 1991

    PubMed  Google Scholar 

  27. Schmidt-Spaniol I, Boldyreff B, Issinger O-G: Isolation and characterization of a monoclonal anti CK-2 alpha subunit antibody of the IgGl subclass. Hybridoma 11: 53–59, 1992

    PubMed  Google Scholar 

  28. Nastainczyk W, Schmidt-Spaniol I, Boldyreff B, Issinger O-G: Isolation and characterization of a monoclonal anti-protein kinase CK2 β-subunit antibody of the IgG class for the direct detection of CK2 β-subunit in tissue cultures of various mammalian species and human tumors. Hybridoma 14: 335–339, 1995

    PubMed  Google Scholar 

  29. Harlow E, Crawford LV, Pim DC, Williamson NM: Monoclonal antibodies specific for the SV40 tumor antigens. J Virol 39: 861–869, 1981

    PubMed  Google Scholar 

  30. Lüscher B, Litchfield DW: Biosynthesis of casein kinase II in lymphoid cell lines. Eur J Biochem 220: 521–526, 1994

    PubMed  Google Scholar 

  31. Prowald A, Schuster N, Montenarh M: Regulation of the DNA binding of p53 by its interaction with protein kinase CK2. FEBS Letters 408: 99–104, 1997

    PubMed  Google Scholar 

  32. Fields S, Jang SK: Presence of a potent transcription activating sequence in the p53 protein. Science 249: 1046–1049, 1990

    PubMed  Google Scholar 

  33. Harris CC: p53 tumor suppressor gene: From the basic research laboratory to the clinic-An abridged historical perspective. Carcinogenesis 17: 1187–1198, 1996

    PubMed  Google Scholar 

  34. Momand J, Zambetti GP, Olson DC, George D, Levine AJ: The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69: 1237–1245, 1992

    PubMed  Google Scholar 

  35. Yew PR, Liu X, Berk AJ: Adenovirus El B oncoprotein tethers a transcriptional repression domain to p53. Genes Dev 8: 190–202, 1994

    PubMed  Google Scholar 

  36. Soussi T: The p53 tumour suppressor gene: a model for molecular epidemiology of human cancer. Molecular Medicine Today 32–37, 1996

  37. Bargonetti J, Reynisdóttir 1, Friedman PN, Prives C: Site-specific binding of wild-type p53 to cellular DNA is inhibited by SV40 T antigen and mutant p53. Genes Dev 6: 1886–1898, 1992

    PubMed  Google Scholar 

  38. Bakalkin G, Yakovieva T, Selivanova G, Magnusson KP, Szekely L, Kiseleva E, Klein G, Terenius L, Wiman KG: p53 Binds single-stranded DNA ends and catalyzes DNA renaturation and strand transfer. Proc Natl Acad Sci USA 91: 413–417, 1994

    PubMed  Google Scholar 

  39. Bakalkin G, Selivanova G, Yakovleva T, Kiseleva E, Kashuba E, Magnusson KP, Szekely L, Klein G, Terenius L, Wiman KG: p53 binds single-stranded DNA ends through the C-terminal domain and internal DNA segments via the middle domain. Nucleic Acids Res 23: 362–369, 1995

    PubMed  Google Scholar 

  40. Cariello NF, Cui L, Beroud C, Soussi T: Database and software for the analysis of mutations in the human p53 gene. Cancer Res 54: 4454–4460, 1994

    PubMed  Google Scholar 

  41. Stürzbecher H-W, Brain R, Addison C, Rudge K, Remm M, Grimaldi M, Keenan E, Jenkins JR: A C-terminal α-helix plus basic region motif is the major structural determinant of p53 tetramerization. Oncogene 7: 1513–1523, 1992

    PubMed  Google Scholar 

  42. Ullrich SJ, Sakaguchi K, Lees-Miller SP, Fiscella M, Mercer WE, Anderson CW, Appella E: Phosphorylation at Ser-15 and Ser-392 in mutant p53 molecules from human tumors is altered compared to wild-type p53. Proc Natl Acad Sci USA 90: 5954–5958, 1993

    PubMed  Google Scholar 

  43. Hupp TR, Lane DP: Allosteric activation of latent p53 tetramers. Curr Biol 4: 865–875, 1994

    PubMed  Google Scholar 

  44. Hupp TR, Lane DP: Regulation of the cryptic sequence-specific DNA-binding function of p53 by protein kinases. Cold Spring Harbor Symp Quant Biol 59: 195–206, 1994

    PubMed  Google Scholar 

  45. Wagner P, Fuchs A, Nastainczyk W: Definition of the p53 binding site on the tms1 protein. Int J Oncol 7: 171–175, 1995

    Google Scholar 

  46. Wang Y, Reed M, Wang P, Stenger JE, Mayr G, Anderson ME, Schwedes JF, Tegtmeyer P: p53 domains: Identification and characterization of two autonomous DNA-binding regions. Genes Dev 7: 2575–2586, 1993

    PubMed  Google Scholar 

  47. Wang Y, Prives C: Increased and altered DNA binding of human p53 by S and G2/M but not G1 cyclin-dependent kinases. Nature 376: 88–91, 1995

    PubMed  Google Scholar 

  48. Clore GM, Omichinski JG, Sakaguchi K, Zambrano N, Sakamoto H, Appelia E, Gronenborn AM: High-resolution structure of the oligomerization domain of p53 by multidimensional NMR. Science 265: 386–391, 1994

    PubMed  Google Scholar 

  49. Jeffrey PD, Gorina S, Pavletich NP: Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 angstroms. Science 267: 1498–1502, 1995

    PubMed  Google Scholar 

  50. Dobner T, Horikoshi N, Rubenwolf S, Shenk T: Blockage by adenovirus E4orf6 of transcriptional activation by the p53 tumor suppressor. Science 272: 1470–1473, 1996

    PubMed  Google Scholar 

  51. Guerra B, Götz C, Wagner P, Montenarh M, Issinger O-G: The carboxy terminus of p53 mimicks the polylysine effect of protein kinase CK2-catalyzed MDM2 phosphorylation. Oncogene 14: 2683–2688, 1997

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Medical Biochemistry, University of the Saarland, Homburg, Germany

    Claudia Götz, Petra Scholtes, Alexandra Prowald, Norbert Schuster, Wolfgang Nastainczyk & Mathias Montenarh

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  1. Claudia Götz
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  2. Petra Scholtes
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  4. Norbert Schuster
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  5. Wolfgang Nastainczyk
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  6. Mathias Montenarh
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Götz, C., Scholtes, P., Prowald, A. et al. Protein kinase CK2 interacts with a multi-protein binding domain of p53. Mol Cell Biochem 191, 111–120 (1999). https://doi.org/10.1023/A:1006886727248

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