NFkB complex translocates from the cytosol to the nucleus

NFkB is a family of transcription factors that play pivotal roles in immune, inflammatory, and antiapoptotic responses. There are five NF-kB/Rel family members, p65 (RelA), RelB, c-Rel, p50/p105 (NF-kappa-B1) and p52/p100 (NFkappa-B2), All members of the NFkB family contain a highly conserved DNA-binding and dimerization domain called Rel-homology region (RHR). The RHR is responsible for homo- or heterodimerization. Therefore, NF-kappa-B exists in unstimulated cells as homo or heterodimers; the most common heterodimer is p65/p50. NF-kappa-B is sequestered in the cytosol of unstimulated cells through the interactions with a class of inhibitor proteins called IkBs, which mask the nuclear localization signal of NF-kB and prevent its nuclear translocation. Various stimuli induce the activation of the IkB kinase (IKK) complex, which then phosphorylates IkBs. The phosphorylated IkBs are ubiquitinated and then degraded through the proteasome-mediated pathway. The degradation of IkBs releases NF-kappa-B and and it can be transported into nucleus where it induces the expression of target genes.<p>DExH/D-box helicase (DHX9)-mediated sensing of CpG-B trigger downstream signaling to NF-κappa B. Knockdown of DHX9 expression by RNA interference in the CpG-B-treated human plasmacytoid dendritic cell line Gen2.2 inhibited nuclear localization of p50 (NF-kappa-B1) subunit of NF-κappa B complex (Kim T et al. 2010).<p>DNA-dependent activator of IRFs/Z-DNA binding protein 1 (ZBP1 or DAI) recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB (Rebsamen M et al. 2009).

NF-kB转录因子家族在免疫、炎症和抗凋亡反应中扮演着至关重要的角色。该家族包含五个成员：p65（RelA）、RelB、c-Rel、p50/p105（NF-kappa-B1）以及p52/p100（NFkappa-B2）。NF-kB家族的所有成员均含有高度保守的DNA结合和二聚化结构域，称为Rel同源区（RHR）。RHR负责同源或异源二聚化。因此，在未受刺激的细胞中，NF-kappa-B以同源或异源二聚体的形式存在；最常见的异源二聚体是p65/p50。未受刺激的细胞中，NF-kappa-B通过与其抑制蛋白IκBs相互作用而被隔离在细胞质中，这些抑制蛋白掩盖了NF-kappa-B的核定位信号，从而阻止其向细胞核的转移。各种刺激可诱导IκB激酶（IKK）复合物的激活，进而磷酸化IκBs。磷酸化的IκBs被泛素化，随后通过蛋白酶体介导的途径降解。IκBs的降解释放NF-kappa-B，使其能够被转运进入细胞核，从而诱导靶基因的表达。<p>DExH/D框螺旋酶（DHX9）介导的CpG-B感知触发下游信号传导至NF-κappa B。通过RNA干扰下调DHX9表达，在CpG-B处理的人浆细胞样树突状细胞系Gen2.2中抑制了NF-κappa B复合物中p50（NF-kappa-B1）亚基的核定位（Kim T等，2010年）。<p>依赖DNA的IRFs激活剂/Z-DNA结合蛋白1（ZBP1或DAI）通过RIP同源相互作用基序招募RIP1和RIP3，以激活NF-kappaB（Rebsamen M等，2009年）。