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泛素化在细胞因子信号转导抑制因子 3(SOCS3)功能和表达调控中的作用。

Role of Ubiquitylation in Controlling Suppressor of Cytokine Signalling 3 (SOCS3) Function and Expression.

机构信息

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK.

出版信息

Cells. 2014 May 30;3(2):546-62. doi: 10.3390/cells3020546.

Abstract

The realisation that unregulated activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is a key driver of a wide range of diseases has identified its components as targets for therapeutic intervention by small molecule inhibitors and biologicals. In this review, we discuss JAK-STAT signalling pathway inhibition by the inducible inhibitor "suppressor of cytokine signaling 3 (SOCS3), its role in diseases such as myeloproliferative disorders, and its function as part of a multi-subunit E3 ubiquitin ligase complex. In addition, we highlight potential applications of these insights into SOCS3-based therapeutic strategies for management of conditions such as vascular re-stenosis associated with acute vascular injury, where there is strong evidence that multiple processes involved in disease progression could be attenuated by localized potentiation of SOCS3 expression levels.

摘要

人们认识到,Janus 激酶-信号转导子和转录激活子(JAK-STAT)通路的不受调节的激活是广泛疾病的关键驱动因素,这将其成分确定为小分子抑制剂和生物制剂治疗干预的靶点。在这篇综述中,我们讨论了可诱导抑制剂“细胞因子信号转导抑制因子 3(SOCS3)”对 JAK-STAT 信号通路的抑制作用,及其在骨髓增生性疾病等疾病中的作用,以及作为多亚基 E3 泛素连接酶复合物的一部分的功能。此外,我们强调了这些基于 SOCS3 的治疗策略在治疗与急性血管损伤相关的血管再狭窄等疾病方面的潜在应用,有强有力的证据表明,疾病进展中涉及的多个过程可以通过局部增强 SOCS3 表达水平来减弱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6abf/4092859/deab6d710301/cells-03-00546-g001.jpg

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