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.

  • Review
  • Published:

Bcl-2 and calcium: controversy beneath the surface

Oncogene volume 23, pages 2875–2880 (2004)Cite this article

Abstract

The function of Bcl-2 family members on the endoplasmic reticulum has received increasing attention in recent years. The endoplasmic reticulum is the major organelle involved in intracellular calcium homeostasis and calcium signaling, including calcium signals that mediate apoptosis induction by anticancer drugs. But currently a controversy exists regarding reported effects of Bcl-2 on the calcium concentration within the lumen of the endoplasmic reticulum. Although several prominent reports indicate that Bcl-2 overexpression is associated with a decrease in luminal calcium, there are a large number of reports indicating that Bcl-2 either does not decrease luminal calcium or actually increases luminal calcium. This review summarizes this vast array of conflicting findings, and analyses potential reasons why different conclusions have been reached by different laboratories. Future directions are emphasized that might bring clarity to this important area of apoptosis biology.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

Similar content being viewed by others

References

  • Baffy G, Miyashita T, Williamson JR and Reed JC . (1993). J. Biol. Chem., 268, 6511–6519.

  • Berridge MJ . (1993). Nature, 361, 315–325.

  • Berridge MJ, Bootman MD and Roderick HL . (2003). Nat. Rev. Mol. Cell Biol., 4, 517–529.

  • Berridge MJ, Lipp P and Bootman MD . (2000). Nat. Rev. Mol. Cell Biol., 1, 11–21.

  • Bian X, Hughes FM, Huang Y, Cidlowski JA and Putney JW . (1997). Am. J. Physiol., 272, (Cell Physiol. 41) C1241–C1249.

  • Bootman MD, Lipp P and Berridge MJ . (2001). J. Cell Sci., 114, 2213–2222.

  • Breckenridge DG, Germain M, Mathai JP, Nuyen M and Shore GC . (2003a). Oncogene, 22, 8608–8618.

  • Breckenridge DG, Nguyen M, Kuppig S, Reth M and Shore GC . (2002). Proc. Natl. Acad. Sci. USA, 99, 4331–4336.

  • Breckenridge DG, Stojanovic M, Marcellus RC and Shore GC . (2003b). J. Cell Biol., 160, 1115–1127.

  • Brostrom CO and Brostrom MA . (1990). Annu. Rev. Physiol., 52, 577–590.

  • Demaurex N and Distelhorst CW . (2003). Science, 300, 65–67.

  • Distelhorst CW, Lam M and McCormick TS . (1996). Oncogene, 12, 2051–2055.

  • Distelhorst CW and McCormick TS . (1996). Cell Calcium, 19, 473–483.

  • Distelhorst CW and Roderick HL . (2003). Biochem. Soc. Trans., 31, 958–959.

  • Foyouzi-Youssefi R, Arnaudeau S, Borner C, Kelley WL, Tschopp J, Lew DP, Demaurex N and Krause KH . (2000). Proc. Natl. Acad. Sci. USA, 97, 5723–5728.

  • Germain M, Mathai JP and Shore GC . (2002). J. Biol. Chem., 277, 18053–18060.

  • Germain M and Shore GC . (2003). Sci. STKE 2003, pe10.

  • Hajnoczky G, Davies E and Madesh M . (2003). Biochem. Biophys. Res. Commun., 304, 445–454.

  • He H, Lam M, McCormick TS and Distelhorst CW . (1997). J. Cell Biol., 138, 1219–1228.

  • Ichimiya M, Chang SH, Liiu H, Berezesky IK, Trump BF and Amstad PA . (1998). Am. J. Physiol., 275, C832–C839.

  • Kaufmann T, Schlipf S, Sanz J, Neubert K, Stein R and Borner C . (2003). J. Cell Biol., 160, 53–64.

  • Kuo TH, Kim H-RC, Zhu L, Yu Y, Lin H-M and Tsang W . (1998). Oncogene, 17, 1903–1910.

  • Lam M, Dubyak G, Chen L, Nuñez G, Miesfeld RL and Distelhorst CW . (1994). Proc. Natl. Acad. Sci. USA, 91, 6569–6573.

  • Li C, Fox CJ, Master SR, Bindokas VP, Chodosh LA and Thompson CB . (2002). Proc. Natl. Acad. Sci. USA, 99, 9830–9835.

  • Liu H, Bowes RCI, van de Water B, Sillence C, Nagelkerke JF and Stevens JL . (1997). J. Biol. Chem., 272, 21751–21759.

  • Lodish HF, Kong N and Wikstrom L . (1992). J. Biol. Chem., 267, 12753–12760.

  • Magnelli L, Cinelli M, Turchetti A and Chiarugi VP . (1994). Biochem. Biophys. Res. Commun., 204, 84–90.

  • Mathai JP, Germain M, Marcellus RC and Shore GC . (2002). Oncogene, 21, 2534–2544.

  • Mery L, Mesaeli N, Michalak M, Opas M, Lew DP and Krause K-H . (1996). J. Biol. Chem., 271, 9332–9339.

  • Nutt LK, Chandra J, Pataer A, Fang B, Roth J, Swisher SG, O’Neil RG and McConkey DJ . (2002). J. Biol. Chem., 277, 20301–20308.

  • Oakes SA, Opferman JT, Pozzan T, Korsmeyer SJ and Scorrano L . (2003). Biochem. Pharm., 66, 1335–1340.

  • Orrenius S, Zhivotovsky B and Nicotera P . (2003). Nat. Rev. Mol. Cell Biol., 4, 552–565.

  • Pan Z, Damron D, Nieminen A-L, Bhatt MB and Ma J . (2000). J. Biol. Chem., 275, 19978–19984.

  • Patel S, Joseph SK and Thomas AP . (1999). Cell Calcium, 25, 247–264.

  • Petersen OH . (2002). Biol. Res., 35, 177–182.

  • Pinton P, Ferrari D, Magalhaes P, Schulze-Osthoff K, Di Virgilio F, Pozzan T and Rizzuto R . (2000). J. Cell Biol., 148, 857–862.

  • Putney Jr JW, Broad LM, Braun FJ, Lievremont JP and Bird GS . (2001). J. Cell Sci., 114, 2223–2229.

  • Rizzuto R, Pinton P, Ferrari D, Chami M, Szabadkai G Magalhaes PJ, Di Virgilio F and Pozzan T . (2003). Oncogene, 22, 8619–8627.

  • Sambrook JF . (1990). Cell, 61, 197–199.

  • Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T and Korsmeyer SJ . (2003). Science, 300, 135139.

  • Shirane M and Nakayama KI . (2003). Nat. Cell Biol., 5, 28–37.

  • Short AD, Bian J, Ghosh TK, Waldron RT and Rybak SL . (1993). Proc. Natl. Acad. Sci. USA, 90, 4986–4990.

  • Thastrup O, Cullen PJ, Drobak BK, Hanley MR and Dawson AP . (1990). Proc. Natl. Acad. Sci., 87, 2466–2470.

  • Thomenius MJ, Wang NS, Reineks EZ, Wang Z and Distelhorst CW . (2003). J. Biol. Chem., 278, 6243–6250.

  • Thrower EC, Hagar RE and Ehrlich BE . (2001). Trends Pharmacol. Sci., 22, 580–586.

  • Uhlmann EJ, Subramanian T, Vater CA, Lutz R and Chinnadurai G . (1998). J. Biol. Chem., 273, 17926–17932.

  • Vanden Abeele F, Skryma R, Shuba Y, Van Coppenolle F, Slomianny C, Roudbaraki M, Mauroy B, Wuytack F and Prevarskaya N . (2002). Cancer Cell, 1, 169–179.

  • Wang NS, Unkila M, Reineks EZ and Distelhorst CW . (2001). J. Biol. Chem., 276, 44117–44128.

  • Wei H, Wei W, Bredesen DE and Perry DC . (1998). J. Neurochem., 70, 2305–2314.

  • Williams SS, French JN, Gilbert M, Rangaswami AA, Walleczek J and Knox SJ . (2000). Cancer Res., 60, 4358–4361.

  • Yu Z, Luo H, Fu W and Mattson MP . (1999). Exp. Neurol., 155, 302–314.

  • Zhong L-T, Sarafian T, Kane DJ, Charles AC, Mah SP, Edwards RH and Bredesen DE . (1993). Proc. Natl. Acad. Sci. USA, 90, 4533–4537.

  • Zhong WX, Li C, Hatzivassiliou G, Lindsten T, Yu Q-C, Yuan J and Thompson CB . (2003). J. Cell Biol., 162, 59–69.

  • Zhu L, Ling S, Yu X-D, Venkatesh LK, Subramanian T, Chinnadurai G and Kuo TH . (1999). J. Biol. Chem., 274, 33267–33273.

Download references

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Comprehensive Cancer Center, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, 44106-4937, OH, USA

    Clark W Distelhorst

  2. Department of Biochemistry and McGill Cancer Center, McGill University, 36555 Promenade Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada

    Gordon C Shore

Authors
  1. Clark W Distelhorst
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gordon C Shore
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clark W Distelhorst.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Distelhorst, C., Shore, G. Bcl-2 and calcium: controversy beneath the surface. Oncogene 23, 2875–2880 (2004). https://doi.org/10.1038/sj.onc.1207519

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207519

Keywords

This article is cited by

Search

Advanced search

Quick links