IkBA 变体导致 EDA-ID
中文名称
通路描述
核因子 kappa B (NFkB) 转录因子家族在细胞质中由 kappa B 家族成员 IKBA (IkB alpha, NFKBIA)、IKBB (IkB beta, NFKBIB) 和 IKBE (IkB epsilon, NFKBIE) 的抑制剂保持无活性。多种刺激，如炎症细胞因子、微生物产物或各种形式的压力，激活 NFkB 信号通路，导致 IkB 分子受到刺激诱导的磷酸化 (Scherer DC 等。1995; Alkalay I 等。1995; Lawrence T 2009; Hoesel B 和 Schmid JA 2013)。IkB 蛋白的磷酸化触发其多聚泛素化，随后被 26S 蛋白酶体降解，允许自由 NFkB 二聚体转位至细胞核，其中指导靶基因的转录。研究已鉴定出一种外胚层发育异常伴免疫缺陷的常染色体显性形式 (AD-EDA-ID)，该病由 NFKBIA/IKBA 基因的超功能杂合突变引起。IKBA 缺陷阻止 IKBA 蛋白的磷酸化和降解，导致获得功能条件，IKBA 在胞质中捕获 NFkB 二聚体的抑制能力增强 (Courtois G 等。2003; Lopes-Granados E 等。2008; Schimke LF 等。2013)。
英文描述
IkBA variant leads to EDA-ID The nuclear factor kappa B (NFkB) family of transcription factors is kept inactive in the cytoplasm by the inhibitor of kappa B (IkB) family members IKBA (IkB alpha, NFKBIA), IKBB (IkB beta, NFKBIB) and IKBE (IkB epsilon, NFKBIE) (Oeckinghaus A and Ghosh S 2009). Multiple stimuli such as inflammatory cytokines, microbial products or various types of stress activate NFkB signaling leading to stimuli-induced phosphorylation of IkB molecule (Scherer DC et al. 1995; Alkalay I et al. 1995; Lawrence T 2009; Hoesel B and Schmid JA 2013). The phosphorylation of IkB proteins triggers their polyubiquitination and subsequent degradation by 26S proteasome, allowing free NFkB dimer to translocate to the nucleus where it directs the expression of target genes. Studies have identified an autosomal dominant form of ectodermal dysplasia with immunodeficiency (AD-EDA-ID) caused by a hypermorphic heterozygous mutation of NFKBIA/IKBA gene. The IKBA defects prevent the phosphorylation and degradation of IKBA protein resulting in gain-of-function condition with the enhanced inhibitory capacity of IKBA in sequestering NF?B dimers in the cytoplasm (Courtois G et al. 2003; Lopes-Granados E et al. 2008; Schimke LF et al. 2013).
所含基因
6 个基因