Article | Published:

Myb DNA binding inhibited by phosphorylation at a site deleted during oncogenic activation

Subjects

Abstract

The c-Myb nuclear oncoprotein is phosphorylated in vitro and in vivo at an N-terminal site near its DNA-binding domain by casein kinase II (CK-II) or a CK-ll-like activity. This in vitro phosphorylation reversibly inhibits the sequence-specific binding of c-Myb to DNA. The site of this phosphorylation is deleted in nearly all oncogenically activated Myb proteins, resulting in DNA-binding that is indepen-dent of CK-II. Because CK-II activity is modulated by growth factors, loss of the site could uncouple c-Myb from its normal physiological regulator.

References

  1. 1

    Klempnauer, K.-H., Symonds, G., Evan, G. & Bishop, J. M. Cell 37, 537–547 (1984).

  2. 2

    Boyle, W. J., Lipsick, J. S. & Baluda, M. A. Proc. natn. Acad. Sci. U.S.A. 83, 4685–4689 (1986).

  3. 3

    Klempnauer, K.-H., Bonifer, C. & Sippel, A. EMBO J. 5, 1903–1911 (1986).

  4. 4

    Boyle, W. J., Lampert, M. A., Li, A. C. & Baluda, M. A. Molec. cell. Biol. 5, 3017–3023 (1985).

  5. 5

    Bading, H., Beutler, C. & Moelling, K. Oncogene 4, 33–38 (1989).

  6. 6

    Clarke, M. F., Kukowska-Latallo, J. F., Westin, E., Smith, M. & Prochownik, E. V. Molec. cell. Biol. 8, 4685–4689 (1988).

  7. 7

    Todokoro, K. et al. Proc. natn. Acad. Sci. U.S.A. 85, 8900–8904 (1988).

  8. 8

    McMahon, J., Howe, K. M. & Watson, R. J. Oncogene 3, 717–720 (1988).

  9. 9

    Duprey, S. P. & Boettiger, D. Proc. natn. Acad. Sci. U.S.A. 82, 6937–6941 (1985).

  10. 10

    Graf, T. & Beug, H. BBA Rev. Cancer 516, 269–299 (1978).

  11. 11

    Beug, H., Blundell, P. A. & Graf, T. Genes Oev. 1, 277–286 (1987).

  12. 12

    Durban, E. M. & Boettiger, D. J. Virol. 37, 488–492 (1981).

  13. 13

    Klempnauer, K.-H. et al. Cell 33, 345–355 (1983).

  14. 14

    Shen-Ong, G. L. C., Potter, M., Mushinski, J. F., Lavu, S. & Reddy, E. P. Science 226, 1077–1080 (1984).

  15. 15

    Kanter, M. R., Smith, R. E. & Hayward, W. S. J. Virol. 62, 1423–1432 (1988).

  16. 16

    Pizer, E. & Humphries, E. H. J. Virol. 63, 1630–1640 (1989).

  17. 17

    Gonda, T. J., Cory, S., Sobieszcuk, P., Holtzman, D. & Adams, J. J. Virol. 61, 2754–2763 (1987).

  18. 18

    Ibanez, C. E. & Lipsick, J. S. J. Virol. 62, 1981–1988 (1988).

  19. 19

    Klempnauer, K.-H. & Sippel, A. E. EMBO J. 6, 2719–2725 (1987).

  20. 20

    Peters, C. W. P., Sippel, A. E., Vingron, M. & Klempnauer, K.-H. EMBO J. 6, 1085–1090 (1987).

  21. 21

    Biedenkapp, H., Borgmeyer, U., Sippel, A. E. & Klempnauer, K.-H. Nature 335, 835–837 (1988).

  22. 22

    Weston, K. & Bishop, J. M. Cell 58, 85–93 (1989).

  23. 23

    Klempnauer, K.-H., Arnold, H. & Biedenkapp, H. Genes Dev. 3, 1582–1589 (1989).

  24. 24

    Sakura, H. et al. Proc. natn. Acad. Sci. U.S.A. 86, 5758–5762 (1989).

  25. 25

    Ness, S. A., Marknell, A. & Graf, T. Cell 59, 1115–1125 (1989).

  26. 26

    Raychaudhuri, P., Bagchi, S. & Nevins, J. R. Genes Dev. 3, 620–627 (1989).

  27. 27

    Yamamoto, K. K., Gonzalez, G. A., Biggs III, W. A. & Montminy, M. R. Nature 334, 494–498 (1988).

  28. 28

    Cyert, M. S. & Thorner, J. Cell 57, 891–893 (1989).

  29. 29

    Edelman, A. M., Blumenthal, D. K. & Krebs, E. G. A. Rev. Biochem. 56, 567–613 (1987).

  30. 30

    Hunter, T. Cell 50, 823–829 (1987).

  31. 31

    Kuenzel, E. A., Mulligan, J. A., Sommercorn, J. & Krebs, E. G. J. biol. Chem. 262, 9136–9140 (1987).

  32. 32

    Krebs, E. G. et al. Cold Spring Harb. Symp. quant. Biol. 53, 77–84 (1988).

  33. 33

    Sommercorn, J., Mulligan, J. A., Lozeman, F. J. & Krebs, E. G. Proc. natn. Acad. Sci. U.S.A. 84, 8834–8838 (1987).

  34. 34

    Klarlund, J. K. & Czech, M. P. J. biol. Chem. 263, 15872–15875 (1988).

  35. 35

    Carroll, D. & Marshak, D. R. J. biol. Chem. 264, 7345–7348 (1989).

  36. 36

    Ackerman, P. & Osheroff, N. J. biol. Chem. 264, 11958–11965 (1989).

  37. 37

    Corvera, S., Roach, P. J., DePadi-Roach, A. A. & Czech, M. P. J. biol. Chem. 263, 3116–3122 (1988).

  38. 38

    Lüscher, B., Kuenzel, E. A., Krebs, E. G. & Eisenman, R. N. EMBO J. 8, 1111–1119 (1989).

  39. 39

    Firzlaff, J. M., Galloway, D. A., Eisenman, R. N. & Lüscher, B. New Biologist 1, 44–53 (1989).

  40. 40

    Luscher, B. & Eisenman, R. N. Molec. cell. Biol. 8, 2504–2512 (1988).

  41. 41

    Meyer, H. E., Hoffman-Pororske, E., Korte, H. & Heilmeyer, L. M. G. Jr FEBS Lett. 204, 61–66 (1986).

  42. 42

    Holmes, C. F. B. FEBS Lett. 215, 21–24 (1987).

  43. 43

    Revzin, A. Bio Techniques 7, 346–355 (1989).

  44. 44

    Lassar, A. B. et al. Cell 58, 823–831 (1989).

  45. 45

    Shen-Ong, G. L. C. & Wolff, L. J. Virol. 61, 3721–3725 (1987).

  46. 46

    Shen-Ong, G. L. C., Lüscher, B. & Eisenman, R. N. Molec. cell. Biol. 9, 5456–5463 (1989).

  47. 47

    Sprang, S. R. et al. Nature 336, 215–221 (1988).

  48. 48

    Howe, K. A., Reakes, C. F. L. & Watson, R. J. EMBO J. 9, 161–169 (1990).

  49. 49

    Metcalf, D. The Molecular Control of Blood Cells (Harvard University Press, 1988).

  50. 50

    Kazlauskas, A. & Cooper, J. A. Cell 58, 1121–1133 (1988).

  51. 51

    Evan, G., Lewis, G. K. & Bishop, J. M. Molec. cell. Biol. 4, 2843–2850 (1989).

  52. 52

    Wempnauer, K.-H. et al. Cell 33, 345–355 (1983).

  53. 53

    Gerondakis, S. & Bishop, J. M. Molec. cell. Biol. 6, 3677–3684 (1986).

  54. 54

    Gonda, T. J., Gough, N. M., Dunn, A. R. & de Blaquiere, J. EMBO J. 4, 2003–2008 (1985).

  55. 55

    Majello, B., Kenvon, L. C. & Dalla-Favera, R. Proc. natn. Acad. Sci. U.S.A. 83, 9636–9640 (1986).

  56. 56

    Weinstein, Y., Cleveland, J. L., Askew, D. S., Rapp, U. R. & Ihle, J. N. J. Virol. 61, 2339–2343 (1987).

Download references

Author information

Rights and permissions

To obtain permission to re-use content from this article visit RightsLink.

About this article

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.