Tristetraprolin as a Therapeutic Target in Inflammatory Disease.

Tristetraprolin as a Therapeutic Target in Inflammatory Disease.
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DOI:
10.1016/j.tips.2016.07.002
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发表时间:
2016-10
影响因子:
13.8
通讯作者:
Blackshear, Perry J.
Blackshear, Perry J.
中科院分区:
医学1区
文献类型:
--
作者:
Patial, Sonika;Blackshear, Perry J.

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RNA结合蛋白的三曲脯氨酸(TTP)家族成员存在于所有主要的真核生物群中。从植物到人类的家族成员可以以高亲和力结合靶mRNA中富含AU的元件。在哺乳动物细胞中,这些蛋白质然后促进靶转录物的去腺苷化和衰变。在小鼠中发现了四种这样的蛋白质,其中研究得最好的是TTP。当它的基因在小鼠中被破坏时,动物会出现严重的关节炎、自身免疫、恶病质、皮炎和骨髓增生综合征。相反,最近的过表达研究已经证明了对免疫炎性疾病的几种实验模型的保护。这种内源性抗炎蛋白可以作为治疗人类类似疾病的新方法的基础。
Members of the tristetraprolin (TTP) family of RNA binding proteins are found in all major eukaryotic groups. Family members from plants through humans can bind AU-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 the mouse, of which the best studied is TTP. When its gene is disrupted in the mouse, 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.
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