Distinct roles of IκB proteins in regulating constitutive NF-κB activity (original) (raw)

Nature Cell Biology volume 7, pages 921–923 (2005)Cite this article

Abstract

The inhibitor of NF-κB (IκB) family of proteins is believed to regulate NF-κB activity by cytoplasmic sequestration. We show that in cells depleted of IκBα, IκBβ and IκBε proteins, a small fraction of p65 binds DNA and leads to constitutive activation of NF-κB target genes, even without stimulation, whereas most of the p65 remains cytoplasmic. These results indicate that although IκBα, IκBβ and IκBε proteins could be dispensable for cytoplasmic retention of NF-κB, they are essential for preventing NF-κB-dependent gene expression in the basal state. We also show that in the absence of IκBα, IκBβ and IκBε proteins, cytoplasmic retention of NF-κB by other cellular proteins renders the pathway unresponsive to activation.

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

Access options

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Buy this article

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

Additional access options:

Similar content being viewed by others

References

  1. Verma, I. M., Stevenson, J. K., Schwarz, E. M., Van Antwerp, D. & Miyamoto, S. Genes Dev. 9, 2723–2735 (1995).
    Article CAS Google Scholar
  2. Hayden, M. S. & Ghosh, S. Genes Dev. 18, 2195–2224 (2004).
    Article CAS Google Scholar
  3. Karin, M. & Ben-Neriah, Y. Annu. Rev. Immunol. 18, 621–663 (2000).
    Article CAS Google Scholar
  4. Bell, S., Matthews, J. R., Jaffray, E. & Hay, R. T. Mol. Cell. Biol. 16, 6477–6485 (1996).
    Article CAS Google Scholar
  5. Tran, K., Merika, M. & Thanos, D. Mol. Cell. Biol. 17, 5386–5399 (1997).
    Article CAS Google Scholar
  6. Klement, J. F. et al. Mol. Cell. Biol. 16, 2341–2349 (1996).
    Article CAS Google Scholar
  7. Beg, A. A., Sha, W. C., Bronson, R. T., Ghosh, S. & Baltimore, D. Nature 376, 167–170 (1995).
    Article CAS Google Scholar
  8. Chen, L. F. & Greene, W. C. Nature Rev. Mol. Cell. Biol. 5, 392–401 (2004).
    Article CAS Google Scholar
  9. Sachdev, S., Hoffmann, A. & Hannink, M. Mol. Cell. Biol. 18, 2524–2534 (1998).
    Article CAS Google Scholar
  10. Tam, W. F., Lee, L. H., Davis, L. & Sen, R. Mol. Cell. Biol. 20, 2269–2284 (2000).
    Article CAS Google Scholar
  11. Prigent, M., Barlat, I., Langen, H. & Dargemont, C. J. Biol. Chem. 275, 36441–36449 (2000).
    Article CAS Google Scholar
  12. Moorthy, A. K. & Ghosh, G. J. Biol. Chem. 278, 556–566 (2003).
    Article CAS Google Scholar
  13. Tergaonkar, V., Bottero, V., Ikawa, M., Li, Q. & Verma, I. M. Mol. Cell. Biol. 23, 8070–8083 (2003).
    Article CAS Google Scholar
  14. Tiscornia, G., Singer, O., Ikawa, M. & Verma, I. M. Proc. Natl Acad. Sci. USA 100, 1844–1848 (2003).
    Article CAS Google Scholar
  15. Memet, S. et al. J. Immunol. 163, 5994–6005 (1999).
    CAS PubMed Google Scholar

Download references

Acknowledgements

We wish to thank A. Hoffmann and D. Baltimore for sharing unpublished information and for insights into this work. We thank C. Rothlin, O. Singer, G. Ghosh, N. Tonnu and B. Coyne for suggestions and help. V.T. is supported by a career development fellowship from the Leukemia and Lymphoma Society. I.M.V. is an American Cancer Society Professor of Molecular Biology and is supported by grants from the NIH, the Wayne and Gladys Valley Foundation, the Larry L. Hillblom Foundation, Inc., the Lebensfeld Foundation, the Merck Research Laboratories and the H.N. and Frances C. Berger Foundation.

Author information

Author notes

  1. Vinay Tergaonkar
    Present address: Institute of Molecular and Cell Biology, 61 Biopolis Drive, 138673, Singapore
  2. Masahito Ikawa
    Present address: Genome information Research Center, Osaka University, 3-1, Osaka, 565-0871, Japan

Authors and Affiliations

  1. Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, 92037, CA, USA
    Vinay Tergaonkar, Ricardo G Correa & Inder M Verma

Authors

  1. Vinay Tergaonkar
    You can also search for this author inPubMed Google Scholar
  2. Ricardo G Correa
    You can also search for this author inPubMed Google Scholar
  3. Masahito Ikawa
    You can also search for this author inPubMed Google Scholar
  4. Inder M Verma
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toInder M Verma.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

About this article

Cite this article

Tergaonkar, V., Correa, R., Ikawa, M. et al. Distinct roles of IκB proteins in regulating constitutive NF-κB activity.Nat Cell Biol 7, 921–923 (2005). https://doi.org/10.1038/ncb1296

Download citation

This article is cited by