TAK-ling IKK activation: "Ub" the judge.
Investigation of the signaling events that lead to the activation of the transcription factor nuclear factor kappaB (NF-kappaB) has been a hotbed for the discovery of previously uncharacterized signaling mechanisms. The important role that nondegradative polyubiquitin chains play in these processes is now well recognized; however, precisely how they orchestrate NF-kappaB signaling is still a matter of much controversy. A recent study has challenged the dogmatic view by demonstrating that interleukin-1beta (IL-1beta), a major proinflammatory cytokine, activates two consecutive pathways, the "RING" and "zinc" pathways, to coordinate early and late activation of NF-kappaB, respectively. This study introduces a paradigm shift in the still-evolving mechanism of regulation of NF-kappaB.
Wuerzberger-Davis
Shelly M
SM
Department of Pharmacology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705, USA.
Miyamoto
Shigeki
S
D000818:Animals; D006801:Humans; D053583:Interleukin-1beta; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D025821:Polyubiquitin / Q000378:metabolism; D015398:Signal Transduction; D000099151:MAP Kinase Kinase Kinase 7
D053583:Interleukin-1beta; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D025821:Polyubiquitin; D000099151:MAP Kinase Kinase Kinase 7