A Chaperone-Like Role for EBI3 in Collaboration With Calnexin Under Inflammatory Conditions.
A Chaperone-Like Role for EBI3 in Collaboration With Calnexin Under Inflammatory Conditions.
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DOI：
10.3389/fimmu.2021.757669
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yoshimoto T
中科院分区：
文献类型：
--
作者：
Watanabe A;Mizoguchi I;Hasegawa H;Katahira Y;Inoue S;Sakamoto E;Furusaka Y;Sekine A;Miyakawa S;Murakami F;Xu M;Yoneto T;Yoshimoto T
白介素 6 (IL-6)/IL-12 细胞因子家族在诱导和调节先天性和适应性免疫反应中发挥着关键作用。在各种细胞因子中，只有该家族具有由两个不同的亚基（α-亚基和β-亚基）组成的独特特征，这两个亚基与其他细胞因子中也存在的亚基形成异二聚体。最近，我们发现α亚基之一——EB病毒诱导基因3（EBI3）在细胞内发挥着新的作用，它可以通过结合其靶蛋白和一种充分表征的凝集素伴侣钙连接蛋白（可能是通过增强伴侣活性）来促进靶蛋白的正确折叠并在蛋白质水平上增强其表达。由于 Calnexin 普遍存在且组成型表达，但 EBI3 表达是诱导型的，因此这些结果可能为建立新范例开辟一条途径，其中 EBI3 在炎症条件下与 Calnexin 合作，在进一步增加蛋白质水平上靶分子的表达方面发挥重要作用。该理论很好地解释了 EBI3 与 p28 形成异二聚体，并且可能与 p35 和 p19 形成异二聚体，分别产生 IL-27、IL-35 和 IL-39。根据这一概念，另一个 β 亚基 p40 在组装诱导的 p35 和 p19 分别产生 IL-12 和 IL-23 的正确折叠中发挥着关键作用。因此，最近强调了正确折叠和成熟中的分子伴侣样活性，其允许分泌具有生物活性的异二聚细胞因子。本综述总结了目前对 EBI3 形成异二聚体和其他关联的分子伴侣活性的理解以及它们可能的生物学意义。
The interleukin-6 (IL-6)/IL-12 family of cytokines plays critical roles in the induction and regulation of innate and adaptive immune responses. Among the various cytokines, only this family has the unique characteristic of being composed of two distinct subunits, α- and β-subunits, which form a heterodimer with subunits that occur in other cytokines as well. Recently, we found a novel intracellular role for one of the α-subunits, Epstein-Barr virus-induced gene 3 (EBI3), in promoting the proper folding of target proteins and augmenting its expression at the protein level by binding to its target protein and a well-characterized lectin chaperone, calnexin, presumably through enhancing chaperone activity. Because calnexin is ubiquitously and constitutively expressed but EBI3 expression is inducible, these results could open an avenue to establish a new paradigm in which EBI3 plays an important role in further increasing the expression of target molecules at the protein level in collaboration with calnexin under inflammatory conditions. This theory well accounts for the heterodimer formation of EBI3 with p28, and probably with p35 and p19 to produce IL-27, IL-35, and IL-39, respectively. In line with this concept, another β-subunit, p40, plays a critical role in the assembly-induced proper folding of p35 and p19 to produce IL-12 and IL-23, respectively. Thus, chaperone-like activities in proper folding and maturation, which allow the secretion of biologically active heterodimeric cytokines, have recently been highlighted. This review summarizes the current understanding of chaperone-like activities of EBI3 to form heterodimers and other associations together with their possible biological implications.
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影响因子：
4.6
作者：
Hasegawa H;Mizoguchi I;Orii N;Inoue S;Katahira Y;Yoneto T;Xu M;Miyazaki T;Yoshimoto T
通讯作者：
Yoshimoto T
DOI：
10.1073/pnas.94.22.12041
发表时间：
1997-10-28
影响因子：
11.1
作者：
Devergne, O;Birkenbach, M;Kieff, E
通讯作者：
Kieff, E
影响因子：
7.2
作者：
Braakman, Ineke;Hebert, Daniel N.
通讯作者：
Hebert, Daniel N.
影响因子：
5.5
作者：
Cassatella, Marco A.;Gardiman, Elisa;Tamassia, Nicola
通讯作者：
Tamassia, Nicola
DOI：
10.1152/ajpgi.00142.2007
发表时间：
2007-12-01
影响因子：
4.5
作者：
Heidemann, Jan;Ruether, Christoph;Maaser, Christian
通讯作者：
Maaser, Christian