RNF31 Regulates Skin Homeostasis by Protecting Epidermal Keratinocytes from Cell Death
RNF31 Regulates Skin Homeostasis by Protecting Epidermal Keratinocytes from Cell Death
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RNF31 通过保护表皮角质细胞免于细胞死亡来调节皮肤稳态。
DOI：
10.4049/jimmunol.1800172
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发表时间：
2018-06-15
影响因子：
4.4
通讯作者：
Lin, Xin
中科院分区：
文献类型：
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作者：
Tang, Yong;Tu, Hailin;Lin, Xin
线性泛素链组装复合物通过用线性（M1连接的）泛素链修饰靶蛋白而在调节TNF-α信号传导激活中起重要作用。在这项研究中，我们报告了表皮特异性敲除（KO）RNF 31，线性泛素链组装复合物的催化亚基，导致小鼠出生后早期的致命性，由于严重的皮肤炎症。炎症主要由TNF-α诱导的RNF 31 KO角质形成细胞凋亡引发。从机制上讲，RNF 31的缺乏不仅损害了TNF-α诱导的NF-kB活化，而且显著增加了细胞凋亡。因此，删除TNF受体1可以挽救RNF 31表皮特异性KO小鼠的死亡率和皮肤炎症。总的来说，我们的研究提供了一个体内的见解，线性泛素化是维持角质形成细胞的稳态，这将有助于设计治疗性化合物来治疗皮肤炎症的关键。
Linear ubiquitin chain assembly complex plays an important role in regulating TNF-alpha signaling activation by modifying target proteins with linear (M1-linked) ubiquitin chains. In this study, we report that the epidermis-specific knockout (KO) of RNF31, the catalytic subunit of linear ubiquitin chain assembly complex, results in an early postnatal lethality in mice due to severe skin inflammation. The inflammation was mainly triggered by TNF-alpha-induced apoptosis in RNF31 KO keratinocytes. Mechanistically, the deficiency of RNF31 not only impaired TNF-alpha-induced NF-kB activation, but also significantly increased apoptosis. Consistently, deleting TNF receptor 1 could rescue the lethality of RNF31 epidermis-specific KO mice and also the skin inflammation. Collectively, our study provides an in vivo insight that linear ubiquitination is critical for maintaining the homeostasis of keratinocytes, which will shed light on designing therapeutic compounds to treat skin inflammation.