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. 1995 Nov;15(11):5966–5974. doi: 10.1128/mcb.15.11.5966

Casein kinase II phosphorylation site mutations in c-Myb affect DNA binding and transcriptional cooperativity with NF-M.

M Oelgeschläger 1, J Krieg 1, J M Lüscher-Firzlaff 1, B Lüscher 1
PMCID: PMC230848  PMID: 7565749

Abstract

Phosphorylation of c-Myb has been implicated in the regulation of the binding of c-Myb to DNA. We show that murine c-Myb is phosphorylated at Ser-11 and -12 in vivo and that these sites can be phosphorylated in vitro by casein kinase II (CKII), analogous to chicken c-Myb. An efficient method to study DNA binding properties of full-length c-Myb and Myb mutants under nondenaturing conditions was developed. It was found that a Myb mutant in which Ser-11 and -12 were replaced with Ala (Myb Ala-11/12), wild-type c-Myb, and Myb Asp-11/12 bound to the A site of the mim-1 promoter with decreasing affinities. In agreement with this finding, Myb Ala-11/12 transactivated better than wild-type c-Myb and Myb Asp-11/12 on the mim-1 promoter or a synthetic Myb-responsive promoter. Similar observations were made for the myeloid-specific neutrophil elastase promoter. The presence of NF-M or an NF-M-like activity abolished partially the differences seen with the Ser-11/12 mutants, suggesting that the reduced DNA binding due to negative charge at positions 11 and 12 can be compensated for by NF-M. Since no direct interaction of c-Myb and NF-M was observed, we propose that the cooperativity is mediated by a third factor. Our data offer two possibilities for how casein kinase II phosphorylation can influence c-Myb function: first, by reducing c-Myb DNA binding and thereby influencing transactivation, and second, by enhancing the apparent cooperativity between c-Myb and NF-M or an NF-M-like activity.

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Selected References

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  1. Arias J., Alberts A. S., Brindle P., Claret F. X., Smeal T., Karin M., Feramisco J., Montminy M. Activation of cAMP and mitogen responsive genes relies on a common nuclear factor. Nature. 1994 Jul 21;370(6486):226–229. doi: 10.1038/370226a0. [DOI] [PubMed] [Google Scholar]
  2. Aziz N., Wu J., Dubendorff J. W., Lipsick J. S., Sturgill T. W., Bender T. P. c-Myb and v-Myb are differentially phosphorylated by p42mapk in vitro. Oncogene. 1993 Aug;8(8):2259–2265. [PubMed] [Google Scholar]
  3. Badiani P., Corbella P., Kioussis D., Marvel J., Weston K. Dominant interfering alleles define a role for c-Myb in T-cell development. Genes Dev. 1994 Apr 1;8(7):770–782. doi: 10.1101/gad.8.7.770. [DOI] [PubMed] [Google Scholar]
  4. Bading H., Beutler C., Moelling K. Mapping of a small phosphopeptide at the carboxyterminus of the viral myb protein by monoclonal antibodies. Oncogene. 1989 Jan;4(1):33–38. [PubMed] [Google Scholar]
  5. Biedenkapp H., Borgmeyer U., Sippel A. E., Klempnauer K. H. Viral myb oncogene encodes a sequence-specific DNA-binding activity. Nature. 1988 Oct 27;335(6193):835–837. doi: 10.1038/335835a0. [DOI] [PubMed] [Google Scholar]
  6. Bousset K., Henriksson M., Lüscher-Firzlaff J. M., Litchfield D. W., Lüscher B. Identification of casein kinase II phosphorylation sites in Max: effects on DNA-binding kinetics of Max homo- and Myc/Max heterodimers. Oncogene. 1993 Dec;8(12):3211–3220. [PubMed] [Google Scholar]
  7. Bousset K., Oelgeschläger M. H., Henriksson M., Schreek S., Burkhardt H., Litchfield D. W., Lüscher-Firzlaff J. M., Lüscher B. Regulation of transcription factors c-Myc, Max, and c-Myb by casein kinase II. Cell Mol Biol Res. 1994;40(5-6):501–511. [PubMed] [Google Scholar]
  8. Bouwmeester T., Güehmann S., el-Baradi T., Kalkbrenner F., van Wijk I., Moelling K., Pieler T. Molecular cloning, expression and in vitro functional characterization of Myb-related proteins in Xenopus. Mech Dev. 1992 Mar;37(1-2):57–68. doi: 10.1016/0925-4773(92)90015-c. [DOI] [PubMed] [Google Scholar]
  9. Burk O., Mink S., Ringwald M., Klempnauer K. H. Synergistic activation of the chicken mim-1 gene by v-myb and C/EBP transcription factors. EMBO J. 1993 May;12(5):2027–2038. doi: 10.1002/j.1460-2075.1993.tb05852.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Calabretta B., Nicolaides N. C. c-myb and growth control. Crit Rev Eukaryot Gene Expr. 1992;2(3):225–235. [PubMed] [Google Scholar]
  11. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chrivia J. C., Kwok R. P., Lamb N., Hagiwara M., Montminy M. R., Goodman R. H. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature. 1993 Oct 28;365(6449):855–859. doi: 10.1038/365855a0. [DOI] [PubMed] [Google Scholar]
  13. Cleveland D. W., Fischer S. G., Kirschner M. W., Laemmli U. K. Peptide mapping by limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis. J Biol Chem. 1977 Feb 10;252(3):1102–1106. [PubMed] [Google Scholar]
  14. Dini P. W., Lipsick J. S. Oncogenic truncation of the first repeat of c-Myb decreases DNA binding in vitro and in vivo. Mol Cell Biol. 1993 Dec;13(12):7334–7348. doi: 10.1128/mcb.13.12.7334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dudek H., Tantravahi R. V., Rao V. N., Reddy E. S., Reddy E. P. Myb and Ets proteins cooperate in transcriptional activation of the mim-1 promoter. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1291–1295. doi: 10.1073/pnas.89.4.1291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Evans J. L., Moore T. L., Kuehl W. M., Bender T., Ting J. P. Functional analysis of c-Myb protein in T-lymphocytic cell lines shows that it trans-activates the c-myc promoter. Mol Cell Biol. 1990 Nov;10(11):5747–5752. doi: 10.1128/mcb.10.11.5747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Firzlaff J. M., Lüscher B., Eisenman R. N. Negative charge at the casein kinase II phosphorylation site is important for transformation but not for Rb protein binding by the E7 protein of human papillomavirus type 16. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5187–5191. doi: 10.1073/pnas.88.12.5187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gabrielsen O. S., Sentenac A., Fromageot P. Specific DNA binding by c-Myb: evidence for a double helix-turn-helix-related motif. Science. 1991 Sep 6;253(5024):1140–1143. doi: 10.1126/science.1887237. [DOI] [PubMed] [Google Scholar]
  19. Gerondakis S., Bishop J. M. Structure of the protein encoded by the chicken proto-oncogene c-myb. Mol Cell Biol. 1986 Nov;6(11):3677–3684. doi: 10.1128/mcb.6.11.3677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gonda T. J., Gough N. M., Dunn A. R., de Blaquiere J. Nucleotide sequence of cDNA clones of the murine myb proto-oncogene. EMBO J. 1985 Aug;4(8):2003–2008. doi: 10.1002/j.1460-2075.1985.tb03884.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Graf T. Myb: a transcriptional activator linking proliferation and differentiation in hematopoietic cells. Curr Opin Genet Dev. 1992 Apr;2(2):249–255. doi: 10.1016/s0959-437x(05)80281-3. [DOI] [PubMed] [Google Scholar]
  22. Hernandez-Munain C., Krangel M. S. Regulation of the T-cell receptor delta enhancer by functional cooperation between c-Myb and core-binding factors. Mol Cell Biol. 1994 Jan;14(1):473–483. doi: 10.1128/mcb.14.1.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Howe K. M., Reakes C. F., Watson R. J. Characterization of the sequence-specific interaction of mouse c-myb protein with DNA. EMBO J. 1990 Jan;9(1):161–169. doi: 10.1002/j.1460-2075.1990.tb08092.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ibanez C. E., Lipsick J. S. trans activation of gene expression by v-myb. Mol Cell Biol. 1990 May;10(5):2285–2293. doi: 10.1128/mcb.10.5.2285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Issinger O. G. Casein kinases: pleiotropic mediators of cellular regulation. Pharmacol Ther. 1993;59(1):1–30. doi: 10.1016/0163-7258(93)90039-g. [DOI] [PubMed] [Google Scholar]
  26. Kalkbrenner F., Guehmann S., Moelling K. Transcriptional activation by human c-myb and v-myb genes. Oncogene. 1990 May;5(5):657–661. [PubMed] [Google Scholar]
  27. Kanter M. R., Smith R. E., Hayward W. S. Rapid induction of B-cell lymphomas: insertional activation of c-myb by avian leukosis virus. J Virol. 1988 Apr;62(4):1423–1432. doi: 10.1128/jvi.62.4.1423-1432.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Katz S., Kowenz-Leutz E., Müller C., Meese K., Ness S. A., Leutz A. The NF-M transcription factor is related to C/EBP beta and plays a role in signal transduction, differentiation and leukemogenesis of avian myelomonocytic cells. EMBO J. 1993 Apr;12(4):1321–1332. doi: 10.1002/j.1460-2075.1993.tb05777.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Klempnauer K. H., Arnold H., Biedenkapp H. Activation of transcription by v-myb: evidence for two different mechanisms. Genes Dev. 1989 Oct;3(10):1582–1589. doi: 10.1101/gad.3.10.1582. [DOI] [PubMed] [Google Scholar]
  30. Klempnauer K. H., Bonifer C., Sippel A. E. Identification and characterization of the protein encoded by the human c-myb proto-oncogene. EMBO J. 1986 Aug;5(8):1903–1911. doi: 10.1002/j.1460-2075.1986.tb04443.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Klempnauer K. H., Sippel A. E. The highly conserved amino-terminal region of the protein encoded by the v-myb oncogene functions as a DNA-binding domain. EMBO J. 1987 Sep;6(9):2719–2725. doi: 10.1002/j.1460-2075.1987.tb02565.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Krieg J., Oelgeschläger M., Janknecht R., Lüscher B. High affinity DNA binding of native full length c-Myb and differential proteolytic sensitivity of its N- and C-terminal domains. Oncogene. 1995 Jun 1;10(11):2221–2228. [PubMed] [Google Scholar]
  33. Ku D. H., Wen S. C., Engelhard A., Nicolaides N. C., Lipson K. E., Marino T. A., Calabretta B. c-myb transactivates cdc2 expression via Myb binding sites in the 5'-flanking region of the human cdc2 gene. J Biol Chem. 1993 Jan 25;268(3):2255–2259. [PubMed] [Google Scholar]
  34. Kwok R. P., Lundblad J. R., Chrivia J. C., Richards J. P., Bächinger H. P., Brennan R. G., Roberts S. G., Green M. R., Goodman R. H. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature. 1994 Jul 21;370(6486):223–226. doi: 10.1038/370223a0. [DOI] [PubMed] [Google Scholar]
  35. Lin A., Frost J., Deng T., Smeal T., al-Alawi N., Kikkawa U., Hunter T., Brenner D., Karin M. Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity. Cell. 1992 Sep 4;70(5):777–789. doi: 10.1016/0092-8674(92)90311-y. [DOI] [PubMed] [Google Scholar]
  36. Litchfield D. W., Dobrowolska G., Krebs E. G. Regulation of casein kinase II by growth factors: a reevaluation. Cell Mol Biol Res. 1994;40(5-6):373–381. [PubMed] [Google Scholar]
  37. Litchfield D. W., Lüscher B. Casein kinase II in signal transduction and cell cycle regulation. Mol Cell Biochem. 1993 Nov;127-128:187–199. doi: 10.1007/BF01076770. [DOI] [PubMed] [Google Scholar]
  38. Lüscher B., Christenson E., Litchfield D. W., Krebs E. G., Eisenman R. N. Myb DNA binding inhibited by phosphorylation at a site deleted during oncogenic activation. Nature. 1990 Apr 5;344(6266):517–522. doi: 10.1038/344517a0. [DOI] [PubMed] [Google Scholar]
  39. Lüscher B., Eisenman R. N. Mitosis-specific phosphorylation of the nuclear oncoproteins Myc and Myb. J Cell Biol. 1992 Aug;118(4):775–784. doi: 10.1083/jcb.118.4.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lüscher B., Eisenman R. N. New light on Myc and Myb. Part II. Myb. Genes Dev. 1990 Dec;4(12B):2235–2241. doi: 10.1101/gad.4.12b.2235. [DOI] [PubMed] [Google Scholar]
  41. Lüscher B., Eisenman R. N. c-myc and c-myb protein degradation: effect of metabolic inhibitors and heat shock. Mol Cell Biol. 1988 Jun;8(6):2504–2512. doi: 10.1128/mcb.8.6.2504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lüscher B., Kuenzel E. A., Krebs E. G., Eisenman R. N. Myc oncoproteins are phosphorylated by casein kinase II. EMBO J. 1989 Apr;8(4):1111–1119. doi: 10.1002/j.1460-2075.1989.tb03481.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Melotti P., Ku D. H., Calabretta B. Regulation of the expression of the hematopoietic stem cell antigen CD34: role of c-myb. J Exp Med. 1994 Mar 1;179(3):1023–1028. doi: 10.1084/jem.179.3.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Mucenski M. L., McLain K., Kier A. B., Swerdlow S. H., Schreiner C. M., Miller T. A., Pietryga D. W., Scott W. J., Jr, Potter S. S. A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Cell. 1991 May 17;65(4):677–689. doi: 10.1016/0092-8674(91)90099-k. [DOI] [PubMed] [Google Scholar]
  45. Mukhopadhyaya R., Wolff L. New sites of proviral integration associated with murine promonocytic leukemias and evidence for alternate modes of c-myb activation. J Virol. 1992 Oct;66(10):6035–6044. doi: 10.1128/jvi.66.10.6035-6044.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Nakagoshi H., Nagase T., Kanei-Ishii C., Ueno Y., Ishii S. Binding of the c-myb proto-oncogene product to the simian virus 40 enhancer stimulates transcription. J Biol Chem. 1990 Feb 25;265(6):3479–3483. [PubMed] [Google Scholar]
  47. Ness S. A., Kowenz-Leutz E., Casini T., Graf T., Leutz A. Myb and NF-M: combinatorial activators of myeloid genes in heterologous cell types. Genes Dev. 1993 May;7(5):749–759. doi: 10.1101/gad.7.5.749. [DOI] [PubMed] [Google Scholar]
  48. Ness S. A., Marknell A., Graf T. The v-myb oncogene product binds to and activates the promyelocyte-specific mim-1 gene. Cell. 1989 Dec 22;59(6):1115–1125. doi: 10.1016/0092-8674(89)90767-8. [DOI] [PubMed] [Google Scholar]
  49. Nicolaides N. C., Gualdi R., Casadevall C., Manzella L., Calabretta B. Positive autoregulation of c-myb expression via Myb binding sites in the 5' flanking region of the human c-myb gene. Mol Cell Biol. 1991 Dec;11(12):6166–6176. doi: 10.1128/mcb.11.12.6166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Nomura N., Takahashi M., Matsui M., Ishii S., Date T., Sasamoto S., Ishizaki R. Isolation of human cDNA clones of myb-related genes, A-myb and B-myb. Nucleic Acids Res. 1988 Dec 9;16(23):11075–11089. doi: 10.1093/nar/16.23.11075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Nordeen S. K. Luciferase reporter gene vectors for analysis of promoters and enhancers. Biotechniques. 1988 May;6(5):454–458. [PubMed] [Google Scholar]
  52. Nuchprayoon I., Meyers S., Scott L. M., Suzow J., Hiebert S., Friedman A. D. PEBP2/CBF, the murine homolog of the human myeloid AML1 and PEBP2 beta/CBF beta proto-oncoproteins, regulates the murine myeloperoxidase and neutrophil elastase genes in immature myeloid cells. Mol Cell Biol. 1994 Aug;14(8):5558–5568. doi: 10.1128/mcb.14.8.5558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Ogata K., Morikawa S., Nakamura H., Sekikawa A., Inoue T., Kanai H., Sarai A., Ishii S., Nishimura Y. Solution structure of a specific DNA complex of the Myb DNA-binding domain with cooperative recognition helices. Cell. 1994 Nov 18;79(4):639–648. doi: 10.1016/0092-8674(94)90549-5. [DOI] [PubMed] [Google Scholar]
  54. Ording E., Kvåvik W., Bostad A., Gabrielsen O. S. Two functionally distinct half sites in the DNA-recognition sequence of the Myb oncoprotein. Eur J Biochem. 1994 May 15;222(1):113–120. doi: 10.1111/j.1432-1033.1994.tb18848.x. [DOI] [PubMed] [Google Scholar]
  55. Peters C. W., Sippel A. E., Vingron M., Klempnauer K. H. Drosophila and vertebrate myb proteins share two conserved regions, one of which functions as a DNA-binding domain. EMBO J. 1987 Oct;6(10):3085–3090. doi: 10.1002/j.1460-2075.1987.tb02616.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. 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]
  57. Pizer E., Humphries E. H. RAV-1 insertional mutagenesis: disruption of the c-myb locus and development of avian B-cell lymphomas. J Virol. 1989 Apr;63(4):1630–1640. doi: 10.1128/jvi.63.4.1630-1640.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Ramsay R. G., Ishii S., Gonda T. J. Increase in specific DNA binding by carboxyl truncation suggests a mechanism for activation of Myb. Oncogene. 1991 Oct;6(10):1875–1879. [PubMed] [Google Scholar]
  59. Ramsay R. G., Ishii S., Gonda T. J. Interaction of the Myb protein with specific DNA binding sites. J Biol Chem. 1992 Mar 15;267(8):5656–5662. [PubMed] [Google Scholar]
  60. Shen-Ong G. L., Morse H. C., 3rd, Potter M., Mushinski J. F. Two modes of c-myb activation in virus-induced mouse myeloid tumors. Mol Cell Biol. 1986 Feb;6(2):380–392. doi: 10.1128/mcb.6.2.380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Shen-Ong G. L. The myb oncogene. Biochim Biophys Acta. 1990 Jun 1;1032(1):39–52. doi: 10.1016/0304-419x(90)90011-o. [DOI] [PubMed] [Google Scholar]
  62. Shen-Ong G. L., Wolff L. Moloney murine leukemia virus-induced myeloid tumors in adult BALB/c mice: requirement of c-myb activation but lack of v-abl involvement. J Virol. 1987 Dec;61(12):3721–3725. doi: 10.1128/jvi.61.12.3721-3725.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Siu G., Wurster A. L., Lipsick J. S., Hedrick S. M. Expression of the CD4 gene requires a Myb transcription factor. Mol Cell Biol. 1992 Apr;12(4):1592–1604. doi: 10.1128/mcb.12.4.1592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Sterneck E., Müller C., Katz S., Leutz A. Autocrine growth induced by kinase type oncogenes in myeloid cells requires AP-1 and NF-M, a myeloid specific, C/EBP-like factor. EMBO J. 1992 Jan;11(1):115–126. doi: 10.1002/j.1460-2075.1992.tb05034.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Sureau A., Soret J., Vellard M., Crochet J., Perbal B. The PR264/c-myb connection: expression of a splicing factor modulated by a nuclear protooncogene. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11683–11687. doi: 10.1073/pnas.89.24.11683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Suzow J., Friedman A. D. The murine myeloperoxidase promoter contains several functional elements, one of which binds a cell type-restricted transcription factor, myeloid nuclear factor 1 (MyNF1). Mol Cell Biol. 1993 Apr;13(4):2141–2151. doi: 10.1128/mcb.13.4.2141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Tanikawa J., Yasukawa T., Enari M., Ogata K., Nishimura Y., Ishii S., Sarai A. Recognition of specific DNA sequences by the c-myb protooncogene product: role of three repeat units in the DNA-binding domain. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9320–9324. doi: 10.1073/pnas.90.20.9320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Weston K., Bishop J. M. Transcriptional activation by the v-myb oncogene and its cellular progenitor, c-myb. Cell. 1989 Jul 14;58(1):85–93. doi: 10.1016/0092-8674(89)90405-4. [DOI] [PubMed] [Google Scholar]
  69. Wolff L., Koller R., Davidson W. Acute myeloid leukemia induction by amphotropic murine retrovirus (4070A): clonal integrations involve c-myb in some but not all leukemias. J Virol. 1991 Jul;65(7):3607–3616. doi: 10.1128/jvi.65.7.3607-3616.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Wolff L., Koller R. Regions of the Moloney murine leukemia virus genome specifically related to induction of promonocytic tumors. J Virol. 1990 Jan;64(1):155–160. doi: 10.1128/jvi.64.1.155-160.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Zobel A., Kalkbrenner F., Guehmann S., Nawrath M., Vorbrueggen G., Moelling K. Interaction of the v-and c-Myb proteins with regulatory sequences of the human c-myc gene. Oncogene. 1991 Aug;6(8):1397–1407. [PubMed] [Google Scholar]

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