Sci. STKE, 15 February 2000
Transcriptional Regulation Directional Phosphorylation Leads to NF-B Activation
The inactive transcription factor NF-B is sequestered in the cytoplasmic compartment through association with the inhibitory molecule IB. IB kinases (IKK) phosphorylate IB whereby NF-B is released and translocates to the nucleus to induce specific gene expression. IKK and IKKβ are critical for the proper regulation of NF-B activity; however, there are conflicting reports on their specific roles. O'Mahony et al. demonstrated that the presence of IKKα in heterodimers with IKKβ inhibits the high basal activity of IKKβ. Signal-activated IKKα phosphorylated and activated IKKβ leading to the derepression of NF-B. This chain of phosphorylation was unidirectional, as IKKβ did not phosphorylate IKKα under the conditions used. The MAP kinase kinase kinase Cot/Tpl-2 also phosphorylated catalytically inactive IKKβ in the absence of IKKα; however, the physiological relevance of this observation is unclear.
O'Mahony, A., Lin, X., Geleziunas, R., and Greene, W.C. (2000) Activation of the heterodimeric IB kinase α (IKKα)-IKKβ complex is directional: IKKα regulates IKKβ under both basal and stimulated conditions. Mol. Cell. Biol. 20: 1170-1178. [Abstract] [Full Text]
Citation: Directional Phosphorylation Leads to NF-B Activation. Sci. STKE 2000, tw5 (2000).
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