The Beginning of the End: IκB Kinase (IKK) and NF-κB Activation

作者：Michael Karin · 发表于：Journal of Biological Chemistry · 年份：1999 · DOI：10.1074/jbc.274.39.27339 · 被引用次数：639 · 研究领域：NF-κB Signaling Pathways、Immune Response and Inflammation、Cytokine Signaling Pathways and Interactions

Rel homology domain nuclear localization sequence tumor necrosis factor interleukin IκB kinase leucine zipper helix-loop-helix IKK complex-associated protein IKK kinase NF-κB/Rel proteins are dimeric, sequence-specific transcription factors that control a variety of important biological decisions from formation of dorsal-ventral polarity in insects to activation of inflammatory and innate immune responses (reviewed in Ref. 1Baeuerle P.A. Baltimore D. Cell. 1996; 87: 13-20Abstract Full Text Full Text PDF PubMed Scopus (2954) Google Scholar). NF-κB proteins are related through the Rel homology domain (RHD),1 which subjects them to a particular type of regulation, centered around nuclear-cytoplasmic shuttling (reviewed in Ref. 2Baldwin A.S. Annu. Rev. Immunol. 1996; 14: 649-681Crossref PubMed Scopus (5649) Google Scholar). The RHD serves several functions. It is the dimerization and DNA binding domain, and we have learned in atomic detail how RHDs dimerize and interact with DNA (3Chen F.E. Huang D-B. Chen Y.-Q. Ghosh G. Nature. 1998; 391: 410-413Crossref PubMed Scopus (342) Google Scholar). In addition, the RHD contains a nuclear localization sequence (NLS), and most importantly it is the site for binding of inhibitors of NF-κB, the IκBs (reviewed in Ref. 2Baldwin A.S. Annu. Rev. Immunol. 1996; 14: 649-681Crossref PubMed Scopus (5649) Google Scholar). The IκBs also form a small family with a core composed of six or more ankyrin repeats, an N-terminal regulatory domain, and a C-t...