Pharmaceutical Chemistry Journal

, Volume 39, Issue 12, pp 621–626 | Cite as

The role of major apoptotic proteins in Ca2+ dependent cell homeostasis

  • E. V. Orlova
  • I. A. Kostanyan
  • V. P. Panov
Molecular-Biological Problems of Drug Design and Mechanism of Drug Action


The key role of Bcl-2 (B-cell lymphoma) family proteins in programmed cell death (apoptosis) is reliably established, but particular molecular mechanisms of downregulation involving these anti-and pro-apoptotic proteins are still insufficiently clear. There are several hypotheses explaining the cell-protective (Bcl-2, Bcl-XL) and pro-apoptotic (Bcl-x, Bak) functions of Bcl-2 family proteins. This paper briefly summarizes the available information concerning the molecular mechanisms of action of the pro-and anti-apoptotic proteins of Bcl-2 family. In particular, an original hypothesis is put forward according to which homo-and heterodimerization of these proteins are the key events in the mechanism of Ca2+ ion dependent homeostasis regulation.


Cell Death Lymphoma Organic Chemistry Molecular Mechanism Family Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    C. Yin, C. M. Knudson, S. J. Korsmeyer, et al., Nature, 385, 637–640 (1997).CrossRefPubMedGoogle Scholar
  2. 2.
    T. Sonoki, H. Matsuzaki, A. Nagasaki, et al., Leukemia, 13, 713–718 (1999).CrossRefPubMedGoogle Scholar
  3. 3.
    M. Lam, G. Dubyak and L. Chen, Proc. Natl. Acad. Sci. USA, 91, 6569–6573 (1994).PubMedGoogle Scholar
  4. 4.
    D. M. Hockenbery, Z. N. Oltvai, X.-M. Yin, et al., Cell, 75, 241–251 (1993).CrossRefPubMedGoogle Scholar
  5. 5.
    H. M. Selinman, J. Biol. Chem., 270, 3487–3490 (1995).Google Scholar
  6. 6.
    C. Richter, FEBS Lett., 325(2), 104–107 (1993).CrossRefPubMedGoogle Scholar
  7. 7.
    J. M. Adams and S. Cory, Science, 281(5350), 1322–1326 (1998).CrossRefPubMedGoogle Scholar
  8. 8.
    S. W. Muchmore, M. Sattler, H. Liang, et al., Nature, 381, 335–341 (1996).CrossRefPubMedGoogle Scholar
  9. 9.
    P. H. Schlesinger, A. Gross, X.-M. Yin, et al., Proc. Natl. Acad. Sci. USA, 94, 11357–11362 (1997).Google Scholar
  10. 10.
    B. Antonsson, F. Conti, A. Ciavatta, et al., Science, 277(5344), 370–372 (1997).CrossRefPubMedGoogle Scholar
  11. 11.
    C. N. Kim, X. Wang, Y. Huang, et al., Cancer Res., 57, 3115–3120 (1997).PubMedGoogle Scholar
  12. 12.
    S. Shimizu, M. Narita and Y. Tsujimoto, Nature, 399, 483–487 (1999).CrossRefPubMedGoogle Scholar
  13. 13.
    M. Loeffler and G. Kroemer, Exp. Cell. Res., 256, 19–26 (2000).CrossRefPubMedGoogle Scholar
  14. 14.
    M. Hirotani, Y. Zhang, N. Fujita, et al., J. Biol. Chem., 274, 20415–20420 (1999).Google Scholar
  15. 15.
    T. Sato, M. Hanada, S. Bodrug, et al., Proc. Natl. Acad. Sci. USA, 91, 9238–9242 (1994).PubMedGoogle Scholar
  16. 16.
    M. Sattler, H. Liang, and D. Nettesheim, Science, 275(5342), 983–986 (1997).CrossRefPubMedGoogle Scholar
  17. 17.
    X.-M. Yin, Z. N. Oltvai, and S. J. Korsmeyer, Nature, 369, 321–323 (1994).CrossRefPubMedGoogle Scholar
  18. 18.
    H. Zha, C. Aime-Sempe, S. Takaaki, et al., J. Biol. Chem., 271, 7440–7444 (1996).CrossRefPubMedGoogle Scholar
  19. 19.
    M. Simonen, H. Keller, and J. Heim, Eur. J. Biochem., 249, 85–91 (1997).CrossRefPubMedGoogle Scholar
  20. 20.
    P. L. Simonian, D. A. Grillot, and G. Nunez, Oncogene, 15(15), 1871–1884 (1997).CrossRefPubMedGoogle Scholar
  21. 21.
    L. Oliver, M. Priault, and K. Tremblais, FEBS Lett., 487(2), 161–165 (2000).CrossRefPubMedGoogle Scholar
  22. 22.
    F. Shibasaki, E. Kondo, T. Akagi, et al., Nature, 386, 728–731 (1997).CrossRefPubMedGoogle Scholar
  23. 23.
    E. A. Permyakov, Calcium-Binding Proteins [in Russian], Nauka, Moscow (1993).Google Scholar
  24. 24.
    H. He, M. Lam, T. S. McCormic, et al., J. Cell Biol., 138, 1219–1228 (1997).CrossRefPubMedGoogle Scholar
  25. 25.
    R. C. Armstrong, T. Aja, J. Xiang, et al., J. Biol. Chem., 271, 16850–16855 (1996).Google Scholar
  26. 26.
    N. Erin, S. K. Bronson, and M. L. Billingsley, Neuroscience, 117(3), 541–555 (2003).CrossRefPubMedGoogle Scholar
  27. 27.
    Y. Liang, K. D. Nylander, and Y. Liang, Mol. Pharmacol., 61(1), 142–149 (2002).CrossRefPubMedGoogle Scholar
  28. 28.
    M. Yabuki, S. Kariya, Y. Inai, et al., Free Radical Res., 27(3), 325–335 (1997).Google Scholar
  29. 29.
    S. Cory, D. C. S. Huang, and J. M. Adams, Oncogen, 22, 8590–8607 (2003).CrossRefGoogle Scholar
  30. 30.
    H. Yamaguchi, K. Bhalla, and H. G. Wang, Cancer Res., 63(7), 1483–1489 (2003).PubMedGoogle Scholar
  31. 31.
    E. H. Cheng, D. G. Kirsch, and R. J. Clem, Science, 278(5345), 1966–196 (1997).CrossRefPubMedGoogle Scholar
  32. 32.
    G. Hajnoczky, E. Davies, and M. Madesh, Biochem. Biophys. Res. Commun., 304(3), 445–454 (2003).CrossRefPubMedGoogle Scholar
  33. 33.
    J. Jia, S. Tarabykina, C. Hansen, et al., Structure (Camb), 9(4), 267–275 (2001).CrossRefGoogle Scholar
  34. 34.
    L. Tartier, Y. L. McCarey, and J. E. Biaglow, Cell Death Differ., 7(10), 1002–1010 (2003).CrossRefGoogle Scholar
  35. 35.
    Y. Teshima, M. Akao, S. P. Jones, et al., Circulation, 108(18), 2275–2281 (2003).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • E. V. Orlova
    • 1
  • I. A. Kostanyan
    • 2
  • V. P. Panov
    • 1
  1. 1.Hematological Research CenterRussian Academy of Medical SciencesMoscowRussia
  2. 2.Shemyakin — Ovchinnikov Institute of Bioorganic ChemistryRussian Academy of SciencesMoscowRussia

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