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:

Induction and endoplasmic reticulum location of BIK/NBK in response to apoptotic signaling by E1A and p53

Oncogene volume 21, pages 2534–2544 (2002)Cite this article

Abstract

A DNA microarray analysis identified the BH3-only BCL-2 family member, BIK/NBK, as a transcript that is upregulated during induction of apoptosis by oncogenic E1A. E1A depended on wild-type p53 to induce BIK and activate the death program. Further, p53 independently induced BIK RNA and protein, and BIK alone stimulated cell death in p53-null cells, dependent on the activation of caspases. BIK function, however, was abrogated by a disabling point mutation within the BH3 domain. Collectively, these results argue that BIK is a downstream apoptotic effector of p53 in response to a physiological p53-mediated death stimulus provided by E1A. Elevated BCL-2 functioned downstream of p53 and BIK induction to inhibit the E1A death pathway, with the ratio of anti-apoptotic BCL-2 and pro-apoptotic BIK determining cell death or survival in E1A-expressing cells. Cells expressing BCL-2 or treated with the pan caspase inhibitor, zVAD-fmk, allowed accumulation of high levels of cytotoxic BIK compared to control cells. Of note, a significant fraction of either ectopic or endogenous BIK was found associated with the endoplasmic reticulum, suggesting that this organelle, in addition to mitochondria, may be a target of BIK function.

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

Similar content being viewed by others

References

  • Aberici A, Moratto D, Benussi L, Gasparini R, Ghidoni LB, Gatta LB, Finazzi D, Frisoni GB, Trabucchi M, Growden JH, Nitsch RM, Binetti G . 1999 J. Biol. Chem. 274: 30764–30769

  • Akao Y, Otsuki Y, Kataoka S, Ito Y, Tsujimoto Y . 1994 Cancer Res. 54: 2468–2471

  • Attardi LD, Reczek EE, Cosmas C, Demicco EG, McCurrach ME, Lowe SW, Jacks T . 2000 Genes Dev. 14: 704–718

  • Bett AJ, Haddara W, Prevec L, Graham FL . 1994 Proc. Natl. Acad. Sci USA 91: 8802–8806

  • Boulakia CA, Chen G, Ng FW, Teodoro JG, Branton PE, Nicholson DW, Poirier GG, Shore GC . 1996 Oncogene 12: 529–535

  • Boyd JM, Gallo GJ, Elangovan B, Houghton AB, Malstrom S, Avery BJ, Ebb RG, Subramanian T, Chittenden T, Lutz RJ, Chinnadurai G . 1995 Oncogene 1: 1921–1928

  • Breckenridge DG, Shore GC . 2000 Crit. Rev. Euk. Gene Exp. 10: 273–280

  • Budihardjo I, Oliver H, Lutter M, Luo X, Wang W . 1999 Annu. Rev. Cell Dev. Biol. 15: 269–290

  • Debbas M, White E . 1993 Genes Dev. 7: 546–554

  • Elangovan B, Chinnadurai G . 1997 J. Biol. Chem. 272: 24494–24498

  • Goping IS, Gross A, Lavoie JN, Nguyen M, Jemmerson R, Roth K, Korsmeyer SJ, Shore GC . 1998 J. Cell Biol. 143: 207–215

  • Gross A, McDonnell JM, Korsmeyer SJ . 1999 Genes Dev. 13: 1899–191l

  • Han J, Sabbatini P, White E . 1996 Mol. Cell Biol. 16: 5857–5864

  • Hedge R, Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Elnemri EM . 1998 J. Biol. Chem. 273: 7783–7786

  • Hengartner MO . 2000 Nature 407: 770–776

  • Huang DCS, Strasser A . 2000 Cell 103: 839–842

  • Jun P, Evan G . 2000 Nat. Med. 5: 498–500

  • Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ, Schlesinger PH . 2000 Cell Death Differ. 12: 166–173

  • Krajewski S, Tanaka S, Takayama S, Schibler M, Fenton W, Reed JC . 1993 Cancer Res. 53: 4701–4714

  • Krammer PH . 2000 Nature 407: 789–795

  • Lin Y, Ma W, Benchimol S . 2000 Nat. Genet. 26: 122–127

  • Lindsten T, Ross AJ, King A, Zong W, Rathmell JC, Shiels HA, Ulrich E, Waymire KG, Mahar R, Frauwirth K, Chen Y, Wei M, Eng VM, Adelman DM, Simon MC, Ma A, Golden JA, Evan G, Korsmeyer SJ, MacGregor GR, Thompson CB . 2000 Mol. Cell. 6: 1389–1399

  • Ljungman M . 2000 Neoplasia 2: 208–225

  • Lowe SW . 1999 Endocr. Relat. Cancer 6: 45–48

  • Lowe SW, Ruley HE . 1993 Genes Dev. 7: 535–545

  • Marshansky V, Wang X, Bertrand R., Luo H, Duguid W, Chinnadura G, Kanaan N, Vu MD, Wu J . 2001 J. Immunol. 166: 3130–3142

  • McGrory WJ, Bautista DS, Graham FL . 1988 J. Virol. 163: 614–617

  • Miyashita T, Reed JC . 1995 Cell 80: 293–299

  • Nakamo K, Vousden KH . 2001 Mol. Cell. 7: 683–694

  • Nakagawa T, Zhu H, Morishimi N, Li E, Xu J, Yankner BA, Yuan J . 2000 Nature 403: 98–103

  • Ng FWH, Nguyen M, Kwan T, Branton PE, Nicholson DW, Cromlish JA, Shore GC . 1997 J. Cell Biol. 139: 327–338

  • Ng FWH, Shore GC . 1998 J. Biol. Chem. 139: 327–338 Mol. Cell. Biol. 20: 6731–6740

  • Nguyen M, Breckenridge DG, Ducret A, Shore GC . 2000 Mol. Cell. Biol. 20: 6731–6740

  • Nguyen M, Walton P, Branton PE, Korsmeyer SJ, Shore GC . 1994 J. Biol. Chem. 269: 16521–16524

  • Nguyen M, Branton PE, Roy S, Nicholson DW, Alnemri ES, Yeh WC, Mak TW, Shore GC . 1998 J. Biol. Chem. 273: 33099–33102

  • Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, Mori T, Nishimor H, Tamai K, Tokino T, Nakamura Y, Taya Y . 2000a Cell 102: 849–862

  • Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N . 2000b Science 288: 1053–1058

  • Orth K, Dixit VM . 1997 J. Biol. Chem. 272: 8841–8844

  • Passer BJ, Pellegrini L, Vito P, Ganjei JK, D'Adamio L . 1999 J. Biol. Chem. 274: 24007–24013

  • Prives C, Hall PA . 1999 J. Pathol. 187: 112–126

  • Querido E, Teodoro JG, Branton PE . 1997 J. Virol. 71: 3526–3533

  • Rao L, Debbas M, Sabbatini P, Hockenbery D, Korsmeyer SJ, White E . 1992 Proc. Natl. Acad. Sci USA 89: 7742–7746

  • Sabbatini P, Han J, Chiou SK, Nicholson DW, White E . 1997 Cell Growth Differ. 8: 643–653

  • Shepherd SE, Howe JE, Mymryk JS, Bayley ST . 1993 J. Virol. 167: 2944–2949

  • Shimizu S, Tsujimoto Y . 2000 Proc. Natl. Acad. Sci USA 97: 577–582

  • Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y . 2000 Oncogene 19: 5736–5746

  • Verma S, Zhao LJ, Chinnadura G . 2001 J. Biol. Chem. 276: 4671–4676

  • Vousden KH . 2000 Cell 103: 691–694

  • Wei MC, Lindsten T, Mootha VK, Weiler S, Gross A, Ashiya M, Thompson CB, Korsmeyer SJ . 2000 Genes Dev. 14: 2060–2071

  • Wei MC, Zong WC, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, Macgregor GR, Thompson CB, Korsmeyer SJ . 2001 Science 292: 727–730

  • White E . 1996 Genes Dev. 10: 1–15

  • Wu GS, Burns TF, McDonald ER, Jiang W, Meng R, Krantz ID, Kao G, Gan DD, Zhou JY, Muschel R, Hamilton SR, Spinner NB, Markowitz S, Wu G, el-Deiry WS . 1997 Nat. Genet. 17: 141–143

  • Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B . 2001 Mol. Cell. 7: 673–682

  • Zong W, Lindsten T, Ross AJ, MacGregor GR, Thompson CB . 2001 Genes Dev. 15: 1481–1486

Download references

Acknowledgements

This work was supported by grants from the National Cancer Institute of Canada and the Canadian Institutes of Health Research. JP Mathai and M Germain hold PhD studentships from CIHR. We are grateful to John Bergeron and Peter Braun for providing antibodies.

Author information

Authors and Affiliations

  1. Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, H3G 1Y6, Quebec, Canada

    Jaigi P Mathai, Marc Germain & Gordon C Shore

  2. GeminX Biotechnologies Inc., Montreal, H2X 3P9, Quebec, Canada

    Richard C Marcellus

Authors
  1. Jaigi P Mathai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marc Germain
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard C Marcellus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gordon C Shore
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gordon C Shore.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mathai, J., Germain, M., Marcellus, R. et al. Induction and endoplasmic reticulum location of BIK/NBK in response to apoptotic signaling by E1A and p53. Oncogene 21, 2534–2544 (2002). https://doi.org/10.1038/sj.onc.1205340

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205340

Keywords

This article is cited by

Search

Advanced search

Quick links