Department of Ophthalmology, University of California, San Francisco, CA 94143, USA.
J Cell Mol Med. 2010 Oct;14(10):2404-14. doi: 10.1111/j.1582-4934.2010.01054.x.
Inhibitor of κB kinase (IKK) gamma (IKKγ), also known as nuclear factor κB (NF-κB) essential modulator (NEMO), is a component of the IKK complex that is essential for the activation of the NF-κB pathway. The NF-κB pathway plays a major role in the regulation of the expression of genes that are involved in immune response, inflammation, cell adhesion, cell survival and development. As part of the IKK complex, IKKγ plays a regulatory role by linking the complex to upstream signalling molecules. IKKγ contains two coiled-coil regions, a leucine zipper domain and a highly conserved zinc finger domain. Mutations affecting IKKγ have been associated with X-linked hypohidrotic ectodermal dysplasia with immune deficiency (HED-ID), with the majority of these mutations affecting the C-terminal region of the protein where the zinc finger is located. The zinc finger of IKKγ is needed for NF-κB activation in a cell- and stimulus-specific manner. The major mechanism by which the zinc finger plays this role appears to be the recognition of polyubiquitinated upstream signalling intermediates. This assertion reinforces the current notion that ubiquitination plays a major role in mediating protein-protein interactions in the NF-κB signalling pathway. Because the zinc finger domain of IKKγ is very likely involved in mediating interactions with ubiquitinated proteins, investigations that look for upstream activators or inhibitors of the IKK complex that bind to and interact with the zinc finger of IKKγ are required to gain a better insight into the exact roles of this domain and into the pathogenesis of HED-ID.
κB 激酶 (IKK) 抑制剂 γ (IKKγ)，也称为核因子 κB (NF-κB) 必需调节剂 (NEMO)，是 IKK 复合物的一个组成部分，对于 NF-κB 途径的激活是必不可少的。NF-κB 途径在调节参与免疫反应、炎症、细胞黏附、细胞存活和发育的基因表达方面起着主要作用。作为 IKK 复合物的一部分，IKKγ 通过将复合物与上游信号分子连接起来发挥调节作用。IKKγ 包含两个卷曲螺旋区、一个亮氨酸拉链结构域和一个高度保守的锌指结构域。影响 IKKγ 的突变与 X 连锁少汗性外胚层发育不良伴免疫缺陷 (HED-ID) 有关，这些突变中的大多数影响位于锌指所在蛋白的 C 末端区域。IKKγ 的锌指以细胞和刺激特异性的方式对于 NF-κB 的激活是必需的。锌指发挥此作用的主要机制似乎是识别多泛素化的上游信号中间物。这一断言加强了泛素化在 NF-κB 信号通路中介导蛋白-蛋白相互作用的重要作用的当前观点。由于 IKKγ 的锌指结构域很可能参与介导与泛素化蛋白的相互作用，因此需要寻找与 IKK 复合物相互作用并与 IKKγ 的锌指相互作用的上游激活剂或抑制剂，以更好地了解该结构域的确切作用和 HED-ID 的发病机制。
