Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Regulation of the mevalonate pathway

Nature volume 343, pages 425–430 (1990)Cite this article

Abstract

The mevalonate pathway produces isoprenoids that are vital for diverse cellular functions, ranging from cholesterol synthesis to growth control. Several mechanisms for feedback regulation of low-density-lipoprotein receptors and of two enzymes involved in mevalonate biosynthesis ensure the production of sufficient mevalonate for several end-products. Manipulation of this regulatory system could be useful in treating certain forms of cancer as well as heart disease.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

References

  1. Hancock, J. F., Magee, A. I., Childs, J. E. & Marshall, C. J. Cell 57, 1167–1177 (1989).

    CAS  PubMed  Google Scholar 

  2. Schafer, W. R. et al. Science 245, 379–385 (1989).

    ADS  CAS  PubMed  Google Scholar 

  3. Casey, P. J., Solski, P. A., Der, C. J. & Buss, J. E. Proc. natn. Acad. Sci. U.S.A. 86, 8323–8327 (1989).

    ADS  CAS  Google Scholar 

  4. Wolda, S. L. & Glomset, J. A. J. biol. Chem. 263, 5997–6000 (1988).

    CAS  PubMed  Google Scholar 

  5. Beck, L. A., Hosick, T. J. & Sinensky, M. J. Cell Biol. 107, 1307–1316 (1988).

    CAS  PubMed  Google Scholar 

  6. Farnsworth, C. C., Wolda, S. L., Gelb, M. H. & Glomset, J. A. J. biol. Chem. 264, 20422–20429 (1989).

    CAS  PubMed  Google Scholar 

  7. Brown, M. S. & Goldstein, J. L. J. Lipid Res. 21, 505–517 (1980).

    CAS  PubMed  Google Scholar 

  8. Goldstein, J. L. & Brown, M. S. J. Lipid Res. 25, 1450–1461 (1984).

    CAS  PubMed  Google Scholar 

  9. Chang, T.-Y. & Limanek, J. S. J. biol. Chem. 255, 7787–7795 (1980).

    CAS  PubMed  Google Scholar 

  10. Clarke, C. F. et al. Molec. cell. Biol. 7, 3138–3146 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Südhof, T. C., Goldstein, J. L., Brown, M. S. & Russell, D. W. Science 228, 815–822 (1985).

    ADS  PubMed  PubMed Central  Google Scholar 

  12. Gil, G., Brown, M. S. & Goldstein, J. L. J. biol. Chem. 261, 3717–3725 (1986).

    CAS  PubMed  Google Scholar 

  13. Reynolds, G. A. et al. Cell 38, 275–286 (1984).

    CAS  PubMed  Google Scholar 

  14. Osborne, T. F., Goldstein, J. L. & Brown, M. S. Cell 42, 203–212 (1985).

    CAS  PubMed  Google Scholar 

  15. Südhof, T. C., Russell, D. W., Brown, M. S. & Goldstein, J. L. Cell 48, 1061–1069 (1987).

    PubMed  Google Scholar 

  16. Südhof, T. C., van der Westhuyzen, D. R., Goldstein, J. L., Brown, M. S. & Russell, D. W. J. biol. Chem. 262, 10773–10779 (1987).

    PubMed  Google Scholar 

  17. Dawson, P. A. et al. J. biol. Chem. 263, 3372–3379 (1988).

    CAS  PubMed  Google Scholar 

  18. Osborne, T. F., Gil, G., Goldstein, J. L. & Brown, M. S. J. biol. Chem. 263, 3380–3387 (1988).

    CAS  PubMed  Google Scholar 

  19. Smith, J. R., Osborne, T. F., Brown, M. S., Goldstein, J. L. & Gil, G. J. biol. Chem. 263, 18480–18487 (1988).

    CAS  PubMed  Google Scholar 

  20. Smith, J. R., Osborne, T. F., Goldstein, J. L. & Brown, M. S. J. biol. Chem. (in the press).

  21. Gil, G., Osborne, T. F., Goldstein, J. L. & Brown, M. S. J. biol. Chem. 263, 19009–19019 (1988).

    CAS  PubMed  Google Scholar 

  22. Gil, G. et al. Proc. natn. Acad. Sci. U.S.A. 85, 8963–8967 (1988).

    ADS  CAS  Google Scholar 

  23. Santoro, C., Mermod, N., Andrews, P. C. & Tjian, R. Nature 334, 218–224 (1988).

    ADS  CAS  PubMed  Google Scholar 

  24. Rajavashisth, T. B., Taylor, A. K., Andalibi, A., Svenson, K. L. & Lusis, A. J. Science 245, 640–643 (1989).

    ADS  CAS  PubMed  Google Scholar 

  25. Endo, A. Klin. Wschr. 66, 421–427 (1988).

    CAS  PubMed  Google Scholar 

  26. Brown, M. S., Faust, J. R., Goldstein, J. L., Kaneko, I. & Endo, A. J. biol. Chem. 253, 1121–1128 (1978).

    CAS  PubMed  Google Scholar 

  27. Nakanishi, M., Goldstein, J. L. & Brown, M. S. J. biol. Chem. 263, 8929–8937 (1988).

    CAS  PubMed  Google Scholar 

  28. Panini, S. R., Schnitzer-Polokoff, R., Spencer, T. A. & Sinensky, M. J. biol. Chem. 264, 11044–11052 (1989).

    CAS  PubMed  Google Scholar 

  29. Chin, D. J. et al. Proc. natn. Acad. Sci. U.S.A. 79, 1185–1189 (1982).

    ADS  CAS  Google Scholar 

  30. Luskey, K. L., Faust, J. R., Chin, D. J., Brown, M. S. & Goldstein, J. L. J. biol. Chem. 258, 8462–8469 (1983).

    CAS  PubMed  Google Scholar 

  31. Chin, D. J. et al. Nature 308, 613–617 (1984).

    ADS  CAS  PubMed  Google Scholar 

  32. Dynan, W. S. Trends Genet. 2, 196–197 (1986).

    CAS  Google Scholar 

  33. Reynolds, G. A., Goldstein, J. L. & Brown, M. S. J. biol. Chem. 260, 10369–10377 (1985).

    CAS  PubMed  Google Scholar 

  34. Hall, R. H. Prog. Nucleic Acid Res. Molec. Biol. 10, 57–86 (1970).

    CAS  Google Scholar 

  35. Liscum, L. et al. J. biol. Chem. 260, 522–530 (1985).

    CAS  PubMed  Google Scholar 

  36. Pathak, R. K., Luskey, K. L. & Anderson, R. G. W. J. Cell Biol. 102, 2158–2168 (1986).

    CAS  PubMed  Google Scholar 

  37. Skalnik, D. G. & Simoni, R. D. DNA 4, 439–444 (1985).

    CAS  PubMed  Google Scholar 

  38. Luskey, K. L. & Stevens, B. J. biol. Chem. 260, 10271–10277 (1985).

    CAS  PubMed  Google Scholar 

  39. Basson, M. E., Thorsness, M. Finer-Moore, J., Stroud, R. M. & Rine, J. Molec. cell. Biol. 8, 3797–3808 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Gertler, F. B., Chiu, C. Y., Richter-Mann, L. & Chin, D. J. Molec. cell. Biol. 8, 2713–2721 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Woodward, H. D., Allen, J. M. C. & Lennarz, W. J. J. biol. Chem. 263, 18411–18418 (1988).

    CAS  PubMed  Google Scholar 

  42. Rajkovic, A., Simonsen, J. N., Davis, R. E. & Rothman, F. M. Proc. natn. Acad. Sci. U.S.A. 86, 8217–8221 (1989).

    ADS  CAS  Google Scholar 

  43. Learned, R. M. & Fink, G. R. Proc. natn. Acad. Sci. U.S.A. 86, 2779–2783 (1989).

    ADS  CAS  Google Scholar 

  44. Dohlman, H. G., Caron, M. G. & Lefkowitz, R. J. Biochemistry 26, 2657–2664 (1987).

    CAS  PubMed  Google Scholar 

  45. Gil, G., Faust, J. R., Chin, D. J., Goldstein, J. L. & Brown, M. S. Cell 41, 249–258 (1985).

    CAS  PubMed  Google Scholar 

  46. Jingami, H., Brown, M. S., Goldstein, J. L., Anderson, R. G. W. & Luskey, K. L. J. Cell Biol. 104, 1693–1704 (1987).

    CAS  PubMed  Google Scholar 

  47. Skalnik, D. G., Narita, H., Kent, C. & Simoni, R. D. J. biol. Chem. 263, 6836–6841 (1988).

    CAS  PubMed  Google Scholar 

  48. Gibson, D. M. in Regulation of HMG CoA Reductase. (ed. Priess, B.) 80–132 (Academic, New York, 1985).

    Google Scholar 

  49. Brown, M. S., Brunschede, G. Y. & Goldstein, J. L. J. biol. Chem. 250, 2502–2509 (1975).

    CAS  PubMed  Google Scholar 

  50. Hardie, D. G., Carling, D. & Sim, A. T. R. Trends biochem. Sci. 14, 20–23 (1989).

    CAS  Google Scholar 

  51. Goldstein, J. L. & Brown, M. S. A. Rev. Biochem. 46, 897–930 (1977).

    CAS  Google Scholar 

  52. Goldstein, J. L., Dana, S. E., Faust, J. R., Beaudet, A. L. & Brown, M. S. J. biol. Chem. 250, 8487–8495 (1975).

    CAS  PubMed  Google Scholar 

  53. Pentchev, P. G. et al. FASEB J. 1, 40–45 (1987).

    CAS  PubMed  Google Scholar 

  54. Liscum, L., Ruggiero, R. M. & Faust, J. R. J. Cell Biol. 108, 1625–1636 (1989).

    CAS  PubMed  Google Scholar 

  55. Kandutsch, A. A., Chen, H. W. & Heiniger, H.-J. Science 201, 498–501 (1978).

    ADS  CAS  PubMed  Google Scholar 

  56. Krieger, M., Goldstein, J. L. & Brown, M. S. Proc. natn. Acad. Sci. U.S.A. 75, 5052–5056 (1978).

    ADS  CAS  Google Scholar 

  57. Dawson, P. A., van der Westhuyzen, D. R., Goldstein, J. L. & Brown, M. S. J. biol. Chem. 264, 9046–9052 (1989).

    CAS  PubMed  Google Scholar 

  58. Dawson, P. A., Ridgway, N. D., Slaughter, C. A., Brown, M. S. & Goldstein, J. L. J. biol. Chem. 264, 16798–16803 (1989).

    CAS  PubMed  Google Scholar 

  59. Taylor, F. R., Saucier, S. E., Shown, E. P., Parish, E. J. & Kandutsch, A. A. J. biol. Chem. 259, 12382–12387 (1984).

    CAS  PubMed  Google Scholar 

  60. Leonard, S. & Sinensky, M. Biochim. biophys. Acta 947, 101–112 (1988).

    CAS  PubMed  Google Scholar 

  61. Metherall, J. E., Goldstein, J. L., Luskey, K. L. & Brown, M. S. J. biol. Chem. 264, 15634–15641 (1989).

    CAS  PubMed  Google Scholar 

  62. Chang, T-Y. & Chang, C. C. Y. Biochemistry 21, 5316–5323 (1982).

    CAS  PubMed  Google Scholar 

  63. Mosley, S. T., Brown, M. S., Anderson, R. G. W. & Goldstein, J. L. J. biol. Chem. 258, 13875–13881 (1983).

    CAS  PubMed  Google Scholar 

  64. Quesney-Huneeus, V., Wiley, M. H. & Siperstein, M. D. Proc. natn. Acad. Sci. U.S.A. 76, 5056–5060 (1979).

    ADS  CAS  Google Scholar 

  65. Habenicht, A. J. R., Glomset, J. A. & Ross, R. J. biol. Chem. 255, 5134–5140 (1980).

    CAS  PubMed  Google Scholar 

  66. Fairbanks, K. P., Witte, L. D. & Goodman, D. S. J. biol. Chem. 259, 1546–1551 (1984).

    CAS  PubMed  Google Scholar 

  67. Maltese, W. A., Aprille, J. R. & Green, R. A. Biochem. J. 246, 441–447 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Schmidt, R. A., Schneider, C. J. & Glomset, J. A. J. biol. Chem. 259, 10175–10180 (1984).

    CAS  PubMed  Google Scholar 

  69. Kamiya, Y., Sakurai, A., Tamura, S. & Takahashi, N. Biochem. biophys. Res. Commun. 83, 1077–1083 (1978).

    CAS  PubMed  Google Scholar 

  70. Kamiya, Y., Sakurai, A., Tamura, S. & Takahashi, N. Agric. Biol. Chem. 43, 1049–1053 (1979).

    CAS  Google Scholar 

  71. Sakagami, Y., Yoshida, M., Isogai, A. & Suzuki, A. Science 212, 1525–1527 (1981).

    ADS  CAS  PubMed  Google Scholar 

  72. Gutierrez, L., Magee, A. I., Marshall, C. J. & Hancock, J. F. EMBO J. 8, 1093–1098 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Clarke, S., Vogel, J. P., Deschenes, R. J. & Stock, J. Proc. natn. Acad. Sci. U.S.A. 85, 4643–4347 (1988).

    ADS  CAS  Google Scholar 

  74. Gruenbaum, Y. et al. J. Cell Biol. 106, 585–596 (1988).

    CAS  PubMed  Google Scholar 

  75. Gibbs, J. B. & Marshall, M. S. Micro. Rev. 53, 171–185 (1989).

    CAS  Google Scholar 

  76. Repko, E. M. & Maltese, W. A. J. biol. Chem. 264, 9945–9952 (1989).

    CAS  PubMed  Google Scholar 

  77. Melancon, P. et al. Cell 51, 1053–1062 (1987).

    CAS  PubMed  Google Scholar 

  78. Goud, B., Salminen, A., Walworth, N. C. & Novick, P. J. Cell 53, 753–768 (1988).

    CAS  PubMed  Google Scholar 

  79. Segev, N., Mulholland, J. & Botstein, D. Cell 52, 915–924 (1988).

    CAS  PubMed  Google Scholar 

  80. Anderson, R. G. W., Orci, L., Brown, M. S., Garcia-Segura, L. M. & Goldstein, J. L. J. Cell Sci. 63, 1–20 (1983).

    CAS  PubMed  Google Scholar 

  81. McGrath, J. P. & Varshavsky, A. Nature 340, 400–404 (1989).

    ADS  CAS  PubMed  Google Scholar 

  82. Brown, M. S. & Goldstein, J. L. Science 232, 34–47 (1986).

    ADS  CAS  PubMed  Google Scholar 

  83. Ma, P. T. S. et al. Proc. natn. Acad. Sci. U.S.A. 83, 8370–8374 (1986).

    ADS  CAS  Google Scholar 

  84. Gil, G., Smith, J. R., Goldstein, J. L. & Brown, M.S. Proc. natn. Acad. Sci. U.S.A. 84, 1863–1866 (1987).

    ADS  CAS  Google Scholar 

  85. Kadonaga, J. T., Jones, K. A. & Tjian, R. Trends biochem. Sci. 11, 20–23 (1986).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Molecular Genetics and Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, 75235, USA

    Joseph L. Goldstein & Michael S. Brown

Authors
  1. Joseph L. Goldstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael S. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Goldstein, J., Brown, M. Regulation of the mevalonate pathway. Nature 343, 425–430 (1990). https://doi.org/10.1038/343425a0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/343425a0

This article is cited by

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.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing