Nuclear factor κB is an important transcription factor that regulates immune responses and skin epithelial development. The proteins that activate latent cytoplasmic NF-κB exist in a huge complex of approximately 900 kD. Two new reports have identified and characterized a new protein (termed Act1 or CIKS) that promotes the activation of NF-κB. Li et al . identified Act1 as a 60-kD protein lacking any obvious catalytic domains, but predicted to contain a helix-loop-helix domain. Constitutive expression of Act1 led to the activation of NF-κB and JNK, in the absence of cellular stimulation. Whereas Li et al . observed that expression of a dominant negative (DN) form of the NF-κB interacting kinase, NIK, could block Act-1-dependent activation of an NF-κB-dependent reporter gene, Leonardi et al . observed a less severe effect mediated by DN-NIK on Act1. Act1 immunoprecipitated with IκB kinase (IKK)γ (also called NEMO) and activated the IKK complex, and Act1 was bound to IKKα and IKKβ but not to NIK (Leonardi et al .), suggesting that Act1 might be influenced by NIK, but in an indirect manner. The helix-loop-helix in the NH 2 -terminal of Act1 was necessary for NF-κB activation and association with the IKK complex. Li, X., Commane, M., Nie, H., Hua, X., Chatterjee-Kishore, M., Wald, D., Haag, M., and Stark, G.R. (2000) Act1, an NF-κB-activating protein. Proc. Natl. Acad. Sci. U.S.A. 97 : 10489-10493. [Abstract] [Full Text] Leonardi, A., Chariot, A., Claudio, E., Cunningham, K., and Siebenlist, U. (2000) CIKS, a connection to IκB kinase and stress-activated protein kinase. Proc. Natl. Acad. Sci. U.S.A . 97 : 10494-10499. [Abstract] [Full Text]