锌指蛋白36作为炎症性疾病的治疗靶点
Tristetraprolin as a Therapeutic Target in Inflammatory Disease.
作者信息
Patial Sonika, Blackshear Perry J
机构信息
Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA; Current address: Louisiana Animal Disease Diagnostic Laboratory (LADDL), School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA; Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
出版信息
Trends Pharmacol Sci. 2016 Oct;37(10):811-821. doi: 10.1016/j.tips.2016.07.002. Epub 2016 Aug 5.
Members of the tristetraprolin (TTP) family of RNA-binding proteins are found in all major eukaryotic groups. TTP family members, from plants through humans, can bind adenosine-uridine rich elements in target mRNAs with high affinity. In mammalian cells, these proteins then promote deadenylation and decay of target transcripts. Four such proteins are found in mice, of which the best studied is TTP. When the gene encoding TTP is disrupted in mice, the animals develop a severe syndrome of arthritis, autoimmunity, cachexia, dermatitis, and myeloid hyperplasia. Conversely, recent overexpression studies have demonstrated protection against several experimental models of immune inflammatory disease. This endogenous anti-inflammatory protein could serve as the basis for novel approaches to therapy of similar conditions in humans.
RNA结合蛋白三磷酸腺苷结合盒转运体（TTP）家族成员存在于所有主要的真核生物类群中。从植物到人类，TTP家族成员能够以高亲和力结合靶mRNA中富含腺苷-尿苷的元件。在哺乳动物细胞中，这些蛋白质随后促进靶转录本的去腺苷酸化和降解。小鼠体内发现了四种这样的蛋白质，其中研究得最深入的是TTP。当编码TTP的基因在小鼠体内被破坏时，动物会出现严重的关节炎、自身免疫、恶病质、皮炎和髓样增生综合征。相反，最近的过表达研究表明，它对几种免疫炎症性疾病的实验模型具有保护作用。这种内源性抗炎蛋白可以作为治疗人类类似疾病新方法的基础。
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