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.

  • Original Paper
  • Published:

Distinct BAG-1 isoforms have different anti-apoptotic functions in BAG-1-transfected C33A human cervical carcinoma cell line

Oncogene volume 21, pages 7050–7059 (2002)Cite this article

Abstract

BAG-1 protein can be expressed as four isoforms of 50, 46, 33 and 29 kDa with different subcellular localizations, which may have different functions in anti-apoptosis, but the exact mechanism remains unclear. We constructed BAG-1 full length and deletion mutated plasmids in a pCR3.1 vector and established stable transfections of BAG-1 isoforms in low BAG-1 expressing C33A cells. Treatment of the transfected cells with cisplatin, staurosporine, paclitaxel and doxorubicine showed that BAG-1 p50, p46 and p33 isoforms enhanced the resistance to apoptosis. BAG-1 p50, p46 and p33 exhibited different degrees of apoptosis inhibition in the transfected cells and BAG-1 p46 isoform had the most pronounced effect on anti-apoptosis. BAG-1 p29 failed to protect the transfected cells from apoptosis. Resistance to apoptosis by BAG-1 isoforms was correlated with decreased caspase-3 activation. We also detected the expression of Bax, Bak, p53, Bcl-2, Bcl-XL, AIF and MRP1 by Western blots. Bcl-2 protein expression was significantly increased in p50, p46 and p33 transfected cells, while the expression of Bax, Bak, p53, Bcl-XL and MRP1 was essentially unchanged. These in vitro results suggest that distinct isoforms of BAG-1 have different anti-apoptotic functions and their functions may be correlated to increased Bcl-2 expression.

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
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  • Adachi M, Torigoe T, Takayama S, Imai K . 1998 Leuk. Lymphoma 30: 483–491

  • Antoku K, Maser RS, Scully Jr WJ, Delach SM, Johnson DE . 2001 Biochem. Biophys. Res. Commun. 286: 1003–1010

  • Bardelli A, Longati P, Albero D, Goruppi S, Schneider C, Ponzetto C, Comoglio PM . 1996 EMBO J. 15: 6205–6212

  • Brimmell M, Burns JS, Munson P, McDonald L, O'Hare MJ, Lakhani SR, Packham G . 1999 Br. J. Cancer 81: 1042–1051

  • Clevenger CV, Thickman K, Ngo W, Chang WP, Takayama S, Reed JC . 1997 Endocrinol. 11: 608–618

  • Crocoll A, Blum M, Cato AC . 2000 Mech. Dev. 91: 355–359

  • Ding Z, Yang X, Chernenko G, Tang SC, Pater A . 2000a Int. J. Cancer 87: 818–823

  • Ding Z, Yang X, Pater A, Tang SC . 2000b Biochem. Biophys. Res. Commun. 270: 415–420

  • Froesch BA, Takayama S, Reed JC . 1998 J. Biol. Chem. 273: 11660–11666

  • Hohfeld J, Jentsch S . 1997 EMBO J. 16: 6209–6216

  • Jänicke RV, Sprengart ML, Wati MR, Porter AG . 1998 J. Biol. Chem. 273: 9357–9360

  • Kullmann M, Schneikert J, Moll J, Heck S, Zeiner M, Gehring U, Cato AC . 1998 J. Biol. Chem. 273: 14620–14625

  • Liu R, Takayama S, Zheng Y, Froesch B, Chen G, Zhang Z, Reed JC, Zhang XK . 1998 J. Biol. Chem. 273: 16985–16992

  • Luders J, Demand J, Schonfelder S, Frien M, Zimmermann R, Hohfeld J . 1998 Biol. Chem. 379: 1217–1226

  • Luders J, Demand J, Höhfeld J . 2000a J. Biol. Chem. 275: 4613–4617

  • Luders J, Demand J, Papp J, Höhfeld J . 2000b J. Biol. Chem. 175: 14817–14823

  • Niyaz Y, Zeiner M, Gehring U . 2001 Cell Sci. 114: 1839–1845

  • Nollen EA, Kabakov AE, Brunsting JF, Kanon B, Hohfeld J, Kampinga HH . 2001 J. Biol. Chem. 276: 4677–4682

  • Rorke S, Murphy S, Khalifa M, Tang SC . 2001 Int. J. Cancer 95: 317–322

  • Schneikert J, Hubner S, Martin E, Cato AC . 1999 J. Cell Biol. 146: 929–940

  • Schulz JB, Bremen D, Reed JC, Lommatzsch J, Takayama S, Wullner U, Loschmann PA, Klockgether T, Weller M . 1997 J. Neurochem. 69: 2075–2086

  • Sondermann H, Scheufler C, Schneider C, Hohfeld J, Hartl FU, Moarefi I . 2001 Science 291: 1553–1557

  • Takahashi N, Sasaki R, Takayashi J, Takayama S, Reed J, Andoh T . 2001 Biochem. Biophys. Res. Commun. 286: 807–814

  • Takayama S, Takaaki S, Krajewski S, Kochel K, Irie S, Millan JA, Reed JC . 1995 Cell 80: 279–284

  • Takayama S, Bimston D, Matsuzawa S, Freeman B, Aime-Sempe C, Xie Z, Morimot R, Reed J . 1997 EMBO J. 16: 4887–4896

  • Takayama S, Xie Z, Reed JC . 1999 J. Biol. Chem. 274: 81–86

  • Tang SC, Shehata N, Chernenko G, Khalifa M, Wang X . 1999 J. Clin. Oncol. 17: 1710–1719

  • Terada S, Fukuoka K, Fujita T, Komatsu T, Takayama S, Reed JC, Suzuki E . 1997 Cytotechnology 25: 17–23

  • Turner BD, Krajewski S, Krajewska M, Takayama S, Gumbs AA, Carter D, Rebbeck TR, Haffty BG, Reed JC . 2001 J. Clin. Oncol. 19: 992–1000

  • Wang H-G, Takayama S, Rapp UR, Reed JC . 1996 Proc. Natl. Acad. Sci. USA 93: 7063–7068

  • Witcher M, Yang X, Pater A, Tang S-C . 2001 Exp. Cell Res. 265: 167–173

  • Yang X, Chernenko G, Hao Y, Ding Z, Pater MM, Pater A, Tang S-C . 1998a Oncogene 17: 981–989

  • Yang X, Hao Y, Pater MM, Tang S-C, Pater A . 1998b Mol. Carcinogen. 22: 95–101

  • Yang X, Hao Y, Pater A, Tang S-C . 1999a Clin. Cancer Res. 5: 1816–1822

  • Yang X, Nakao Y, Pater M, Tang S-C, Pater A . 1997 J. Cell Biochem. 66: 309–321

  • Yang X, Pater A, Tang S-C . 1999b Oncogene 18: 4546–4553

  • Zapata JM, Krajewska M, Krajewski S, Huang RP, Takayama S, Wang HG, Adamson E, Reed JC . 1998 Breast Cancer Res. Treat. 47: 129–140

  • Zeiner M, Gehring U . 1995 Proc. Natl. Acad. Sci. USA 92: 11465–11469

  • Zeiner M, Gebauer M, Gehring U . 1997 EMBO J. 16: 5483–5490

  • Zeiner M, Niyaz Y, Gehring U . 1999 Proc. Natl. Acad. Sci. USA 96: 10194–10199

Download references

Acknowledgements

These investigations were supported by grants from the Canadian Breast Cancer Research Initiative and the Canadian Institutes of Health Research.

Author information

Authors and Affiliations

  1. Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's, A1B 3V6, NF, Canada

    Jun Chen, Jieying Xiong, Hongyu Liu & Garry Chernenko

  2. University of Miami Sylvester Comprehensive Cancer Center, 1475 N.W. 12th Avenue, Miami, 33136, Florida, FL, USA

    Shou-Ching Tang

Authors
  1. Jun Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jieying Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hongyu Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Garry Chernenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shou-Ching Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shou-Ching Tang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, J., Xiong, J., Liu, H. et al. Distinct BAG-1 isoforms have different anti-apoptotic functions in BAG-1-transfected C33A human cervical carcinoma cell line. Oncogene 21, 7050–7059 (2002). https://doi.org/10.1038/sj.onc.1205845

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205845

Keywords

This article is cited by

Search

Advanced search

Quick links