IKKα, A Histone Kinase

Science's STKE  10 Jun 2003:
Vol. 2003, Issue 186, pp. tw217-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 κB (IκB) kinase (IKK) complex binds the promoters of specific genes regulated by signals, such as tumor necrosis factor-α (TNF-α), that stimulate nuclear factor κB (NF-κB) activity. IKKα, in response to TNF-α treatment of cultured cells, accumulated in the nucleus and bound to NF-κB-regulated gene promoters such as in the interleukin (IL)-8 and IL-6 genes and the IκBα 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-κB-regulated genes was diminished. Thus, the function of IKKα appears to have expanded beyond its role in activating latent NF-κB 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 IκB kinase-α in NF-κB-dependent gene expression. Nature 423, 659-663 (2003). [Online Journal]

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