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. 1996 May 15;316(Pt 1):331–335. doi: 10.1042/bj3160331

Casein kinase 2 inhibits the renaturation of complementary DNA strands mediated by p53 protein.

O Filhol 1, J Baudier 1, E M Chambaz 1, C Cochet 1
PMCID: PMC1217343  PMID: 8645226

Abstract

Considerable effort is currently being devoted to understand the functions of protein p53, a major regulator of cell proliferation. The protein p53 has been reported to catalyse the annealing of complementary DNA or RNA strands. We report that this activity is inhibited in the presence of the serine/threonine protein kinase CK2. It is shown that this inhibition can be explained by the occurrence of a high-affinity molecular association between p53 and CK2. The molecular complex involves an interaction between the C-terminal domain of p53 and the beta subunit of the oligomeric kinase. Accordingly, the isolated alpha subunit of the kinase was without effect. In addition, after phosphorylation by CK2, phosphorylated p53 lost its DNA annealing activity. Because the C-terminal domain of p53 is both involved in the association with CK2 and phosphorylated by it, our results suggest that either protein-protein interaction or phosphorylation of this domain might control the base pairing of complementary sequences promoted by p53 in processes related to DNA replication and repair.

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Selected References

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  1. Allende J. E., Allende C. C. Protein kinases. 4. Protein kinase CK2: an enzyme with multiple substrates and a puzzling regulation. FASEB J. 1995 Mar;9(5):313–323. doi: 10.1096/fasebj.9.5.7896000. [DOI] [PubMed] [Google Scholar]
  2. Bakalkin G., Selivanova G., Yakovleva T., Kiseleva E., Kashuba E., Magnusson K. P., Szekely L., Klein G., Terenius L., Wiman K. G. p53 binds single-stranded DNA ends through the C-terminal domain and internal DNA segments via the middle domain. Nucleic Acids Res. 1995 Feb 11;23(3):362–369. doi: 10.1093/nar/23.3.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bakalkin G., Yakovleva T., Selivanova G., Magnusson K. P., Szekely L., Kiseleva E., Klein G., Terenius L., Wiman K. G. p53 binds single-stranded DNA ends and catalyzes DNA renaturation and strand transfer. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):413–417. doi: 10.1073/pnas.91.1.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bargonetti J., Reynisdóttir I., Friedman P. N., Prives C. Site-specific binding of wild-type p53 to cellular DNA is inhibited by SV40 T antigen and mutant p53. Genes Dev. 1992 Oct;6(10):1886–1898. doi: 10.1101/gad.6.10.1886. [DOI] [PubMed] [Google Scholar]
  5. Baudier J., Delphin C., Grunwald D., Khochbin S., Lawrence J. J. Characterization of the tumor suppressor protein p53 as a protein kinase C substrate and a S100b-binding protein. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11627–11631. doi: 10.1073/pnas.89.23.11627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bischoff J. R., Friedman P. N., Marshak D. R., Prives C., Beach D. Human p53 is phosphorylated by p60-cdc2 and cyclin B-cdc2. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4766–4770. doi: 10.1073/pnas.87.12.4766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brain R., Jenkins J. R. Human p53 directs DNA strand reassociation and is photolabelled by 8-azido ATP. Oncogene. 1994 Jun;9(6):1775–1780. [PubMed] [Google Scholar]
  8. Filhol O., Baudier J., Delphin C., Loue-Mackenbach P., Chambaz E. M., Cochet C. Casein kinase II and the tumor suppressor protein P53 associate in a molecular complex that is negatively regulated upon P53 phosphorylation. J Biol Chem. 1992 Oct 15;267(29):20577–20583. [PubMed] [Google Scholar]
  9. Filhol O., Cochet C., Chambaz E. M. Cytoplasmic and nuclear distribution of casein kinase II: characterization of the enzyme uptake by bovine adrenocortical nuclear preparation. Biochemistry. 1990 Oct 23;29(42):9928–9936. doi: 10.1021/bi00494a025. [DOI] [PubMed] [Google Scholar]
  10. Filhol O., Cochet C., Wedegaertner P., Gill G. N., Chambaz E. M. Coexpression of both alpha and beta subunits is required for assembly of regulated casein kinase II. Biochemistry. 1991 Nov 19;30(46):11133–11140. doi: 10.1021/bi00110a016. [DOI] [PubMed] [Google Scholar]
  11. Finlay C. A., Hinds P. W., Levine A. J. The p53 proto-oncogene can act as a suppressor of transformation. Cell. 1989 Jun 30;57(7):1083–1093. doi: 10.1016/0092-8674(89)90045-7. [DOI] [PubMed] [Google Scholar]
  12. Fiscella M., Zambrano N., Ullrich S. J., Unger T., Lin D., Cho B., Mercer W. E., Anderson C. W., Appella E. The carboxy-terminal serine 392 phosphorylation site of human p53 is not required for wild-type activities. Oncogene. 1994 Nov;9(11):3249–3257. [PubMed] [Google Scholar]
  13. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  14. Hsu Y. S., Tang F. M., Liu W. L., Chuang J. Y., Lai M. Y., Lin Y. S. Transcriptional regulation by p53. Functional interactions among multiple regulatory domains. J Biol Chem. 1995 Mar 24;270(12):6966–6974. doi: 10.1074/jbc.270.12.6966. [DOI] [PubMed] [Google Scholar]
  15. Hupp T. R., Meek D. W., Midgley C. A., Lane D. P. Activation of the cryptic DNA binding function of mutant forms of p53. Nucleic Acids Res. 1993 Jul 11;21(14):3167–3174. doi: 10.1093/nar/21.14.3167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hupp T. R., Meek D. W., Midgley C. A., Lane D. P. Regulation of the specific DNA binding function of p53. Cell. 1992 Nov 27;71(5):875–886. doi: 10.1016/0092-8674(92)90562-q. [DOI] [PubMed] [Google Scholar]
  17. Jamal S., Ziff E. B. Raf phosphorylates p53 in vitro and potentiates p53-dependent transcriptional transactivation in vivo. Oncogene. 1995 Jun 1;10(11):2095–2101. [PubMed] [Google Scholar]
  18. Jayaraman J., Prives C. Activation of p53 sequence-specific DNA binding by short single strands of DNA requires the p53 C-terminus. Cell. 1995 Jun 30;81(7):1021–1029. doi: 10.1016/s0092-8674(05)80007-8. [DOI] [PubMed] [Google Scholar]
  19. Kern S. E., Kinzler K. W., Bruskin A., Jarosz D., Friedman P., Prives C., Vogelstein B. Identification of p53 as a sequence-specific DNA-binding protein. Science. 1991 Jun 21;252(5013):1708–1711. doi: 10.1126/science.2047879. [DOI] [PubMed] [Google Scholar]
  20. Lane D. P. Cancer. p53, guardian of the genome. Nature. 1992 Jul 2;358(6381):15–16. doi: 10.1038/358015a0. [DOI] [PubMed] [Google Scholar]
  21. Lane D. P., Crawford L. V. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261–263. doi: 10.1038/278261a0. [DOI] [PubMed] [Google Scholar]
  22. Lane D. P. p53 in Paris, an oncogene comes of age. Oncogene. 1987;1(3):241–242. [PubMed] [Google Scholar]
  23. Lee S., Elenbaas B., Levine A., Griffith J. p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell. 1995 Jun 30;81(7):1013–1020. doi: 10.1016/s0092-8674(05)80006-6. [DOI] [PubMed] [Google Scholar]
  24. Levine A. J., Momand J., Finlay C. A. The p53 tumour suppressor gene. Nature. 1991 Jun 6;351(6326):453–456. doi: 10.1038/351453a0. [DOI] [PubMed] [Google Scholar]
  25. Meek D. W., Simon S., Kikkawa U., Eckhart W. The p53 tumour suppressor protein is phosphorylated at serine 389 by casein kinase II. EMBO J. 1990 Oct;9(10):3253–3260. doi: 10.1002/j.1460-2075.1990.tb07524.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Meisner H., Czech M. P. Phosphorylation of transcriptional factors and cell-cycle-dependent proteins by casein kinase II. Curr Opin Cell Biol. 1991 Jun;3(3):474–483. doi: 10.1016/0955-0674(91)90076-b. [DOI] [PubMed] [Google Scholar]
  27. Milne D. M., Campbell L. E., Campbell D. G., Meek D. W. p53 is phosphorylated in vitro and in vivo by an ultraviolet radiation-induced protein kinase characteristic of the c-Jun kinase, JNK1. J Biol Chem. 1995 Mar 10;270(10):5511–5518. doi: 10.1074/jbc.270.10.5511. [DOI] [PubMed] [Google Scholar]
  28. Milne D. M., Palmer R. H., Campbell D. G., Meek D. W. Phosphorylation of the p53 tumour-suppressor protein at three N-terminal sites by a novel casein kinase I-like enzyme. Oncogene. 1992 Jul;7(7):1361–1369. [PubMed] [Google Scholar]
  29. Milne D. M., Palmer R. H., Meek D. W. Mutation of the casein kinase II phosphorylation site abolishes the anti-proliferative activity of p53. Nucleic Acids Res. 1992 Nov 11;20(21):5565–5570. doi: 10.1093/nar/20.21.5565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Momand J., Zambetti G. P., Olson D. C., George D., Levine A. J. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell. 1992 Jun 26;69(7):1237–1245. doi: 10.1016/0092-8674(92)90644-r. [DOI] [PubMed] [Google Scholar]
  31. Müller E., Boldyreff B., Scheidtmann K. H. Characterization of protein kinase activities associated with p53-large-T immune complexes from SV40-transformed rat cells. Oncogene. 1993 Aug;8(8):2193–2205. [PubMed] [Google Scholar]
  32. Oberosler P., Hloch P., Ramsperger U., Stahl H. p53-catalyzed annealing of complementary single-stranded nucleic acids. EMBO J. 1993 Jun;12(6):2389–2396. doi: 10.1002/j.1460-2075.1993.tb05893.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Padmanabha R., Chen-Wu J. L., Hanna D. E., Glover C. V. Isolation, sequencing, and disruption of the yeast CKA2 gene: casein kinase II is essential for viability in Saccharomyces cerevisiae. Mol Cell Biol. 1990 Aug;10(8):4089–4099. doi: 10.1128/mcb.10.8.4089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Pinna L. A. Casein kinase 2: an 'eminence grise' in cellular regulation? Biochim Biophys Acta. 1990 Sep 24;1054(3):267–284. doi: 10.1016/0167-4889(90)90098-x. [DOI] [PubMed] [Google Scholar]
  35. Reed M., Woelker B., Wang P., Wang Y., Anderson M. E., Tegtmeyer P. The C-terminal domain of p53 recognizes DNA damaged by ionizing radiation. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9455–9459. doi: 10.1073/pnas.92.21.9455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rolley N., Milner J. Specific DNA binding by p53 is independent of mutation at serine 389, the casein kinase II site. Oncogene. 1994 Oct;9(10):3067–3070. [PubMed] [Google Scholar]
  37. Seldin D. C., Leder P. Casein kinase II alpha transgene-induced murine lymphoma: relation to theileriosis in cattle. Science. 1995 Feb 10;267(5199):894–897. doi: 10.1126/science.7846532. [DOI] [PubMed] [Google Scholar]
  38. Shaulsky G., Ben-Ze'ev A., Rotter V. Subcellular distribution of the p53 protein during the cell cycle of Balb/c 3T3 cells. Oncogene. 1990 Nov;5(11):1707–1711. [PubMed] [Google Scholar]
  39. Steinmeyer K., Deppert W. DNA binding properties of murine p53. Oncogene. 1988 Nov;3(5):501–507. [PubMed] [Google Scholar]
  40. Vogelstein B., Kinzler K. W. p53 function and dysfunction. Cell. 1992 Aug 21;70(4):523–526. doi: 10.1016/0092-8674(92)90421-8. [DOI] [PubMed] [Google Scholar]
  41. Wang Y., Eckhart W. Phosphorylation sites in the amino-terminal region of mouse p53. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4231–4235. doi: 10.1073/pnas.89.10.4231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wu L., Bayle J. H., Elenbaas B., Pavletich N. P., Levine A. J. Alternatively spliced forms in the carboxy-terminal domain of the p53 protein regulate its ability to promote annealing of complementary single strands of nucleic acids. Mol Cell Biol. 1995 Jan;15(1):497–504. doi: 10.1128/mcb.15.1.497. [DOI] [PMC free article] [PubMed] [Google Scholar]

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