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Sci. STKE, 10 June 2003
Vol. 2003, Issue 186, p. tw217
[DOI: 10.1126/stke.2003.186.tw217]



Two groups (Yamamoto et al. and Anest et al.) show that one of the kinases, IKKα, in the inhibitor of {kappa}B (I{kappa}B) kinase (IKK) complex binds the promoters of specific genes regulated by signals, such as tumor necrosis factor-α (TNF-α), that stimulate nuclear factor {kappa}B (NF-{kappa}B) activity. IKKα, in response to TNF-α treatment of cultured cells, accumulated in the nucleus and bound to NF-{kappa}B-regulated gene promoters such as in the interleukin (IL)-8 and IL-6 genes and the I{kappa}Bα gene. Furthermore, IKKα stimulated phosphorylation of histone 3 on serine 10, and in cells deficient in IKKα histone phosphorylation was decreased and TNF-α-stimulated expression of NF-{kappa}B-regulated genes was diminished. Thus, the function of IKKα appears to have expanded beyond its role in activating latent NF-{kappa}B to a role in directly phosphorylating the promoters of selected genes to contribute to stimulation of gene expression (see Israël).

Y. Yamamoto, U. N. Verma, S. Prajapati, Y.-T. Kwak, R. B. Gaynor, Histone H3 phosphorylation by IKK-α is critical for cytokine-induced gene expression. Nature 423, 655-659 (2003). [Online Journal]

V. Anest, J. L. Hanson, P. C. Cogswell, K. A. Steinbrecher, B. D. Strahl, A. S. Baldwin, A nucleosomal function for I{kappa}B kinase-α in NF-{kappa}B-dependent gene expression. Nature 423, 659-663 (2003). [Online Journal]

A. Israël, A regulator branches out. Nature 423, 596-597 (2003). [Online Journal]

Citation: IKKα, A Histone Kinase. Sci. STKE 2003, tw217 (2003).

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