TRANSCRIPTION IKK, A Histone Kinase

Two groups (Yamamoto et al. and Anest et al.) show that one of the kinases, IKK, in the inhibitor of B (IB) kinase (IKK) complex binds the promoters of specific genes regulated by signals, such as tumor necrosis factor- (TNF-), that stimulate nuclear factor B (NF-B) activity. IKK, in response to TNF- treatment of cultured cells, accumulated in the nucleus and bound to NF-B-regulated gene promoters such as in the interleukin (IL)-8 and IL-6 genes and the IB gene. Furthermore, IKK stimulated phosphorylation of histone 3 on serine 10, and in cells deficient in IKK histone phosphorylation was decreased and TNF--stimulated expression of NF-B-regulated genes was diminished. Thus, the function of IKK appears to have expanded beyond its role in activating latent NF-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- 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 IB kinase- in NF-B-dependent gene expression. Nature 423, 659-663 (2003). [Online Journal]

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