Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omorinishi, Ota-ku, Tokyo 143-8540, Japan.
Cells. 2024 Aug 31;13(17):1467. doi: 10.3390/cells13171467.
More than a decade after the discovery of the classical cytoplasmic IκB proteins, IκBζ was identified as an additional member of the IκB family. Unlike cytoplasmic IκB proteins, IκBζ has distinct features, including its nuclear localization, preferential binding to NF-κB subunits, unique expression properties, and specialized role in NF-κB regulation. While the activation of NF-κB is primarily controlled by cytoplasmic IκB members at the level of nuclear entry, IκBζ provides an additional layer of NF-κB regulation in the nucleus, enabling selective gene activation. Human genome-wide association studies (GWAS) and gene knockout experiments in mice have elucidated the physiological and pathological roles of IκBζ. Despite the initial focus to its role in activated macrophages, IκBζ has since been recognized as a key player in the IL-17-triggered production of immune molecules in epithelial cells, which has garnered significant clinical interest. Recent research has also unveiled a novel molecular function of IκBζ, linking NF-κB and the POU transcription factors through its N-terminal region, whose role had remained elusive for many years.
在经典细胞质 IκB 蛋白被发现十多年后，IκBζ 被鉴定为 IκB 家族的另一个成员。与细胞质 IκB 蛋白不同，IκBζ 具有独特的特征，包括核定位、优先与 NF-κB 亚基结合、独特的表达特性以及在 NF-κB 调节中的专门作用。虽然 NF-κB 的激活主要通过细胞质 IκB 成员在核内进入水平上进行控制，但 IκBζ 在核内提供了 NF-κB 调节的额外层次，实现了选择性基因激活。人类全基因组关联研究 (GWAS) 和小鼠基因敲除实验阐明了 IκBζ 的生理和病理作用。尽管最初的研究重点是其在激活的巨噬细胞中的作用，但 IκBζ 已被认为是上皮细胞中 IL-17 触发免疫分子产生的关键因子，这引起了广泛的临床关注。最近的研究还揭示了 IκBζ 的一个新的分子功能，通过其 N 端区域将 NF-κB 和 POU 转录因子联系起来，其作用多年来一直难以捉摸。
