ISG15, an interferon-stimulated ubiquitin-like protein, is not essential for STAT1 signaling and responses against vesicular stomatitis and lymphocytic choriomeningitis virus
ISG15, an interferon-stimulated ubiquitin-like protein, is not essential for STAT1 signaling and responses against vesicular stomatitis and lymphocytic choriomeningitis virus
复制标题
DOI：
10.1128/mcb.25.15.6338-6345.2005
复制
发表时间：
2005-08-01
影响因子：
5.3
通讯作者：
Knobeloch, KP
中科院分区：
文献类型：
--
作者：
Osiak, A;Utermöhlen, O;Knobeloch, KP
ISG 15是一种干扰素诱导的泛素样修饰物，可以与不同的但大部分未知的蛋白质缀合。ISG 15与多种生物学活性有关，包括抗病毒防御、免疫应答和妊娠。缺乏UBP 43（USP 18）（ISG 15-解结合酶）的小鼠会产生严重的脑损伤表型和对poly（I：C）的致死性超敏反应。据报道，在不存在UBP 43的情况下增加的ISG 15缀合诱导了延长的STAT 1磷酸化，并且ISG 15缀合在JAK/STAT和干扰素信号传导的调节中起重要作用（O. A. Malakhova，M.严，M. P. Malakhov，Y. Yuan，K. J.里奇，K. I.金湖，澳-地F. Peterson，K. Shuai和D. E. Zhang，Genes Dev. 17：455-460，2003）。在这里，我们报告说，ISG 15（-/-）小鼠是可行的和可生育的，并显示没有明显的异常。缺乏ISG 15不会影响免疫系统主要细胞区室的发育和组成。干扰素诱导的抗病毒状态和针对水泡性口炎病毒和淋巴细胞性脉络丛脑膜炎病毒的免疫应答在不存在ISG 15的情况下没有显著改变。此外，干扰素或内毒素诱导的STAT 1酪氨酸磷酸化，以及典型的STAT 1靶基因的表达，仍然不受缺乏ISG 15的影响。因此，ISG 15是STAT 1和干扰素信号传导的载体。
ISG15 is an interferon-induced ubiquitin-like modifier which can be conjugated to distinct, but largely unknown, proteins. ISG15 has been implicated in a variety of biological activities, which encompass antiviral defense, immune responses, and pregnancy. Mice lacking UBP43 (USP18), the ISG15-deconjugating enzyme, develop a severe phenotype with brain injuries and lethal hypersensitivity to poly(I:C). It has been reported that an augmented conjugation of ISG15 in the absence of UBP43 induces prolonged STAT1 phosphorylation and that the ISG15 conjugation plays an important role in the regulation of JAK/STAT and interferon signaling (O. A. Malakhova, M. Yan, M. P. Malakhov, Y. Yuan, K. J. Ritchie, K. I. Kim, L. F. Peterson, K. Shuai, and D. E. Zhang, Genes Dev. 17:455-460, 2003). Here, we report that ISG15(-/-) mice are viable and fertile and display no obvious abnormalities. Lack of ISG15 did not affect the development and composition of the main cellular compartments of the immune system. The interferon-induced antiviral state and immune responses directed against vesicular stomatitis virus and lymphocytic choriomeningitis virus were not significantly altered in the absence of ISG15. Furthermore, interferon- or endotoxin-induced STAT1 tyrosine-phosphorylation, as well as expression of typical STAT1 target genes, remained unaffected by the lack of ISG15. Thus, ISG15 is dispensable for STAT1 and interferon signaling.