Editors' ChoiceTranscription

The NEMO Connection

STKE  28 Mar 2000:
Vol. 2000, Issue 25, pp. tw5
DOI: 10.1126/stke.2000.25.tw5

The cytokine tumor necrosis factor (TNF) activates the transcription factor NF-κB through recruitment of the adaptor protein RIP to the TNF receptor and eventual activation of the I-κ-B-kinase (IKK) "signalosome," a macromolecular complex that alleviates the inhibitory effects of IκB proteins on NF-κB. Zhang et al. now show that, when activated, the TNF receptor induces binding of RIP to NEMO, a core component of the signalosome, and this interaction results in the recruitment of the signalosome to the TNF receptor. TNF treatment of cells also stimulated NEMO interaction with A20, a protein that inhibits NF-κB. The authors propose that NEMO's interaction with various signaling molecules may allow it to translocate the signalosome to specific signaling complexes at appropriate times.

Zhang, S.Q., Kovalenko, A., Cantarella, G., and Walach, D. (2000) Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKγ) upon receptor stimulation. Immunity 12: 301-311. [Online Journal]