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Ubiquitin protein modification and signal transduction: implications for inflammatory bowel diseases.

机译:泛素蛋白修饰和信号转导:对炎症性肠病的影响。

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摘要

A dysregulated immune response to luminal antigen(s) is associated with the development of inflammatory bowel diseases (IBDs). A complex network of inflammatory and immune mediators released by immune and nonimmune cells participate in the physiopathology of IBD. At the molecular level, events leading to the improper use of the signaling grid are likely responsible for the dysregulated activation of various transcription factors and subsequent induction of inflammatory genes. The posttranslational modification of signaling proteins by the ubiquitin system is a critical event in activation or repression of transcription factors. Two important transcriptional pathways in which ubiquitin is central are the nuclear factor-kappaB and hypoxia inducible factor-1 (HIF-1) pathways, both of which are important components of intestinal homeostasis. In this review, we discuss the role of ubiquitin modification in relation to nuclear factor-kappaB and HIF-1 signaling and consider its impact on intestinal inflammation. A greater understanding of posttranslational ubiquitin modification may lead to the identification of new therapeutic opportunities for the treatment of IBD.
机译:对腔抗原的免疫反应失调与炎症性肠病(IBD)的发展有关。由免疫和非免疫细胞释放的炎性和免疫介质的复杂网络参与了IBD的生理病理学。在分子水平上,导致信号网格使用不当的事件可能是导致各种转录因子激活失调以及随后诱发炎症基因的原因。泛素系统对信号蛋白的翻译后修饰是转录因子激活或抑制中的关键事件。泛素在其中很重要的两个重要转录途径是核因子-κB和缺氧诱导因子-1(HIF-1)途径,它们都是肠道稳态的重要组成部分。在这篇综述中,我们讨论了泛素修饰与核因子-κB和HIF-1信号传导相关的作用,并考虑了其对肠道炎症的影响。对翻译后泛素修饰的更多了解可能会导致鉴定出治疗IBD的新治疗机会。

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