CHUK, IKBKB and IKBKG form IKK complex

The multimeric I kappa B kinase (IKK) complex is a key regulator of NF-kappa-B signaling, which is responsible for the phosphorylation of inhibitor kB (IkB). The phosphorylation by IKK triggers K48-linked ubiquitination of IkB leading to proteasomal degradation of IkB, allowing translocation of NFkB factor to the nucleus, where it can activate transcription of a variety of genes participating in the immune and inflammatory response, cell adhesion, growth control, and protection against apoptosis (Alkalay I et al. 1995; Collins T et al. 1995; Kaltschmidt B et al. 2000; Oeckinghaus A and Ghosh S 2009). The IKK complex is composed of the two catalytic subunits, IKKa (IKBKA, IKK1 or CHUK) and IKKb (IKK2 or IKBKB) kinases, and a regulatory subunit, NF-kappa-B essential modulator (NEMO, IKKg or IKBKG). IKBKG (NEMO) associates with the C-termini of unphosphorylated IKKs and promotes the IKK complex activation (Rothwarf DM et al. 1998). The molecular composition and stoichiometry of the IKK complex remains debatable, although the core IKK complex that range from 700 to 900 kDa is thought to consist of an IKBKA:IKBKB heterodimer associated with an IKBKG dimer or higher oligomeric assemblies (DiDonato JA et al. 1997; May J et al. 2002; Tegethoff S et al. 2003; Marienfeld RB et al. 2006; Rushe M et al. 2008).

多聚性IκB激酶（IKK）复合物是NF-κB信号传导的关键调控因子，该信号传导负责抑制性kB（IkB）的磷酸化。IKK的磷酸化作用触发了IkB的K48连接泛素化，导致IkB的蛋白酶体降解，从而允许NFkB因子转移至细胞核，在那里它可以激活参与免疫和炎症反应、细胞粘附、生长调控以及对凋亡的抵抗的多种基因的转录（Alkalay I等人，1995；Collins T等人，1995；Kaltschmidt B等人，2000；Oeckinghaus A和Ghosh S，2009）。IKK复合物由两个催化亚基，IKKa（IKBKA、IKK1或CHUK）和IKKb（IKK2或IKBKB）激酶，以及一个调节亚基，NF-κB必需调节因子（NEMO、IKKg或IKBKG）组成。IKBKG（NEMO）与未磷酸化的IKK的C端结合，并促进IKK复合物的激活（Rothwarf DM等人，1998）。尽管核心IKK复合物的分子组成和化学计量比尚有争议，但认为其核心复合物，分子量在700至900kDa之间，由一个IKBKA:IKBKB异源二聚体与一个IKBKG二聚体或更高阶的寡聚组装体相结合（DiDonato JA等人，1997；May J等人，2002；Tegethoff S等人，2003；Marienfeld RB等人，2006；Rushe M等人，2008）。