Relationship between inflammation and novel NF-κB activation pathway which is regulated by ubiquitin system

LUBAC泛素连接酶由SHARPIN、HOIL-1 L和HOIP组成，形成一种新型的线性多聚泛素链。LUBAC调节NF-κB系统，NF-κ B系统是炎症和免疫调节的关键转录因子。此外，我们还发现，由于自发突变而缺乏Sharpen的cpdm小鼠，通过LUBAC和NF-κB活性的降低而诱导皮炎。这些结果表明，线性多聚泛素化是NF-κB活化的一个不可或缺的转录后修饰。

We identified LUBAC ubiquitin ligase, which composed of SHARPIN, HOIL-1L, and HOIP, forms a novel type of linear polyubiquitin chain. LUBAC regulates NF-κB system, a critical transcription factor for inflammation and immune regulation. Furthermore, we revealed that cpdm mice, which lack Sharpen by a spontaneous mutation, induce dermatitis by the reduction of LUBAC and NF-κB activity. These results indicate that linear polyubiquitination is an indispensable post-transcription modification for NF-κB activation.