University Clinic Freiburg, Department of Neuropathology, Freiburg im Breisgau, Germany.
Biochem Biophys Res Commun. 2012 Jan 6;417(1):135-40. doi: 10.1016/j.bbrc.2011.11.071. Epub 2011 Nov 23.
Posttranslational protein modification by ubiquitin and ubiquitin-like modifiers (UBLs) is mediated by a hierarchical cascade of conjugating enzymes and affects multiple biological processes within the cell. Interferon-stimulated gene 15 (ISG15) is an UBL, which is strongly induced by type I Interferon and ISG15 modification was shown to play an essential role in antiviral defense. While hHERC5 is the major E3 ligase for ISG15 modification in humans, ISGylation in the murine systems at the level of E3 ligases was weakly characterized as rodent genomes lack a direct homologue of hHERC5. Here, we show that mHERC6 is strongly induced by different pathogen-associated molecular patterns (PAMPs) in a type I Interferon receptor (IFNAR1) dependent manner. We demonstrate that mHERC6 is essential for endogenous murine ISGylation and thus represents the dominant ISG15 E3 ligase in mice. In contrast to its human homologue, mHERC6 is also capable to mediate conjugation of human ISG15.
泛素和泛素样修饰物（UBLs）的翻译后蛋白修饰是由一系列级联连接酶介导的，影响细胞内的多种生物过程。干扰素刺激基因 15（ISG15）是一种 UBL，它被 I 型干扰素强烈诱导，并且 ISG15 的修饰在抗病毒防御中起着至关重要的作用。虽然 hHERC5 是人类中 ISG15 修饰的主要 E3 连接酶，但在鼠类系统中 E3 连接酶水平的 ISGylation 特征较弱，因为啮齿动物基因组缺乏 hHERC5 的直接同源物。在这里，我们表明 mHERC6 以 I 型干扰素受体（IFNAR1）依赖性方式被不同的病原体相关分子模式（PAMPs）强烈诱导。我们证明 mHERC6 对内源性鼠类 ISGylation 是必需的，因此代表了小鼠中主要的 ISG15 E3 连接酶。与人类同源物不同，mHERC6 还能够介导人 ISG15 的缀合。
