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Science 25 June 2004:
Vol. 304. no. 5679, pp. 1963 - 1967
DOI: 10.1126/science.1098387
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Reports

Activation of Transcription Factor NF-{kappa}B Requires ELKS, an I{kappa}B Kinase Regulatory Subunit

Jeanette L. Ducut Sigala,1 Virginie Bottero,1 David B. Young,2 Andrej Shevchenko,3 Frank Mercurio,2 Inder M. Verma1*

The nuclear factor–kappa B (NF-{kappa}B) family of transcription factors plays a seminal role in inflammation, apoptosis, development, and cancer. Modulation of NF-{kappa}B–mediated gene expression in response to diverse signals is coordinated by the I{kappa}B kinase (IKK) complex. We identified ELKS, an essential regulatory subunit of the IKK complex. Silencing ELKS expression by RNA interference blocked induced expression of NF-{kappa}B target genes, including the NF-{kappa}B inhibitor I{kappa}B{alpha} and proinflammatory genes such as cyclo-oxygenase 2 and interleukin 8. These cells were also not protected from apoptosis in response to cytokines. ELKS likely functions by recruiting I{kappa}B{alpha} to the IKK complex and thus serves a regulatory function for IKK activation.

1 The Salk Institute for Biological Sciences, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Celgene, 4550 Towne Centre Court, San Diego, CA 92121, USA.
3 Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.

* To whom correspondence should be addressed. E-mail: verma{at}salk.edu

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