Skip to main content

Advertisement

SpringerLink
Log in

Differential effects of NF-κB on apoptosis induced by DNA-damaging agents: the type of DNA damage determines the final outcome

  • Original Article
  • Published:
Oncogene Submit manuscript

Abstract

The transcription factor nuclear factor kappa-B (NF-κB) is generally regarded as an antiapoptotic factor. Accordingly, NF-κB activation inhibits death ligand-induced apoptosis. In contrast, ultraviolet light B (UVB)-induced apoptosis is not inhibited but even enhanced upon NF-κB activation by interleukin-1 (IL-1). This study was performed to identify the molecular mechanisms underlying this switch of NF-κB. Enhancement of UVB-induced apoptosis was always associated with increased release of tumour necrosis factor-α (TNF-α), which was dependent on NF-κB activation. The same was observed when UVA and cisplatin were used, which like UVB induce base modifications. In contrast, apoptosis caused by DNA strand breaks was not enhanced by IL-1, indicating that the type of DNA damage is critical for switching the effect of NF-κB on apoptosis. Surprisingly, activated NF-κB induced TNF-α mRNA expression in the presence of all DNA damage-inducing agents. However, in the presence of DNA strand breaks, there was no release of the TNF-α protein, which is so crucial for enhancing apoptosis. Together, this indicates that induction of DNA damage may have a significant impact on biological effects but it is the type of DNA damage that determines the final outcome. This may have implications for the role of NF-κB in carcinogenesis and for the application of NF-κB inhibitors in anticancer therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

Abbreviations

IκBα:

inhibitor of kappa-B

IKK:

IκB kinase

IL-1:

interleukin-1

NF-κB:

nuclear factor kappa-B

TNF-α:

tumor necrosis factor-α

References

  • Abdel-Raheem IT, Hide I, Yanase Y, Shigemoto-Mogami Y, Sakai N, Shirai Y et al. (2005). Br J Pharmacol 145: 415–423.

  • Armstrong BK, Kricker A . (2001). J Photochem Photobiol 63: 8–18.

  • Beissert S, Schwarz T . (1999). J Invest Dermatol Symp Proc 4: 61–64.

  • Besaratinia A, Synold TW, Chen HH, Chang C, Xi B, Riggs AD et al. (2005). Proc Natl Acad Sci USA 102: 10058–10063.

  • Bohuslav J, Chen L-F, Kwon H, Mu Y, Greene WC . (2004). J Biol Chem 279: 26115–26125.

  • Campbell KJ, Rocha S, Perkins N . (2004). Mol Cell 13: 853–865.

  • Chomczynski P, Sacchi N . (1987). Anal Biochem 162: 156–159.

  • Cornelius S, Bruynooghe Y, Van Loo G, Saelens X, Vandenbeele P, Bayaert R . (2005). Oncogene 24: 1552–1562.

  • Dixit V, Mak TW . (2002). Cell 111: 615–619.

  • Fisher GJ, Datta SC, Talwar HS, Wang ZQ, Varani J, Kang S et al. (1996). Nature 379: 335–339.

  • Fries W, Beyaert R, Declerq W, Vandenabeele P . (1999). Oncogene 18: 7719–7730.

  • Hailer MK, Slade PG, Martin BD, Rosenquist TA, Sugden KD . (2005). DNA Repair 4: 41–50.

  • Ho WC, Dickson KM, Barker PA . (2005). Cancer Res 65: 4273–4280.

  • Hoeijmakers JH . (2001). Nature 411: 366–374.

  • Hur GM, Lewis J, Yang Q, Lin Y, Nakano H, Nedospasov S et al. (2003). Genes Dev 17: 873–882.

  • Konemann S, Bolling T, Kolkmeyer A, Riesenbeck D, Hesselmann S, Vormoor J et al. (2005). Apoptosis 10: 177–184.

  • Kothny-Wilkes G, Kulms D, Pöppelmann B, Luger TA, Kubin M, Schwarz T . (1998). J Biol Chem 273: 29247–29253.

  • Kothny-Wilkes G, Kulms D, Luger TA, Kubin M, Schwarz T . (1999). J Biol Chem 274: 28916–28921.

  • Kulms D, Pöppelmann B, Schwarz T . (2000). J Biol Chem 275: 15060–15066.

  • Kulms D, Pöppelmann B, Yarosh D, Luger T A, Krutmann J, Schwarz T . (1999). Proc Natl Acad Sci USA 96: 7974–7979.

  • Kulms D, Schwarz T . (2002). Biochem Pharmacol 64: 837–841.

  • Kulms D, Zeise E, Pöppelmann B, Schwarz T . (2002). Oncogene 21: 5844–5851.

  • Lee JY, Hannun YA, Obeid LM . (2000). J Biol Chem 275: 29290–29298.

  • Mezyk R, Bzowska M, Bereta J . (2003). Acta Biochim Pol 50: 625–645.

  • Nakajima S, Lan L, Kanno S, Takao M, Yamamoto K, Eker AP et al. (2004). J Biol Chem 279: 46674–46677.

  • Panta GR, Kaur S, Cavin LG, Cortés ML, Mercurio F, Lothstein L et al. (2004). Mol Cell Biol 24: 1823–1835.

  • Pöppelmann B, Klimmek K, Strozyk E, Voss R, Schwarz T, Kulms D . (2005). J Biol Chem 280: 15635–15643.

  • Rosell R, Taron M, Barnadas A, Scagliotti G, Sarries C, Roig B . (2003). Cancer Control 10: 297–305.

  • Ryan KM, Ernst MK, Rice NR, Vousden KH . (2000). Nature 404: 892–897.

  • Sclabas GM, Uwagawa T, Schmidt C, Hess KR, Evans DB, Abbruzzese JL et al. (2005). Cancer 103: 2485–2490.

  • Sordet O, Kahn QA, Kohn KW, Pommier Y . (2003). Curr Med Chem 3: 271–290.

  • Sun NK, Huang SL, Lin-Chao S, Chao CCK . (1996). Biochem J 313: 441–445.

  • Thanos D, Maniatis T . (1995). Cell 80: 529–532.

  • Thoma B, Grell M, Pfizenmaier K, Scheurich P . (1990). J Exp Med 172: 1019–1023.

  • Thyss R, Virolle V, Imbert V, Peyron J-F, Aberdam D, Virolle T . (2005). EMBO J 24: 128–137.

  • Wajant H, Gerspach J, Pfizenmaier K . (2005). Cytokine Growth Factor Rev 16: 55–76.

  • Xu C, Shen G, Chen C, Gelinas C, Kong AN . (2005). Oncogene 24: 4486–4495.

  • Zavarski I, Jakob C, Schmid P, Krebbel H, Kaiser M, Fleissner C et al. (2005). Anticancer Drugs 16: 475–481.

Download references

Acknowledgements

We are greatful to P Scheurich, Institue of Cellbiology and Immunology, University of Stuttgart, for generous supply of FACS antibodies and antagonistic anti-TNF-R1 Fab. We thank N Peters, University of Stuttgart for exellent technical support and H Grothuesmann, University of Münster, for assistance with γ-irradiation of cells. This work was funded by the German Research Foundation, SFB 415/A16, The Federal Ministry of Environmental Protection St.Sch_4491 and the Ceries Award 2004 to TS.

Author information

Authors and Affiliations

  1. Department of Dermatology, University of Muenster, Muenster, Germany

    E Strozyk & B Pöppelmann

  2. Department of Dermatology, University of Kiel, Kiel, Germany

    T Schwarz

  3. Department of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany

    D Kulms

Authors
  1. E Strozyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B Pöppelmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Schwarz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D Kulms
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D Kulms.

Additional information

Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Strozyk, E., Pöppelmann, B., Schwarz, T. et al. Differential effects of NF-κB on apoptosis induced by DNA-damaging agents: the type of DNA damage determines the final outcome. Oncogene 25, 6239–6251 (2006). https://doi.org/10.1038/sj.onc.1209655

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209655

  • Springer Nature Limited

Keywords

This article is cited by

Search

Navigation