Deubiquitinases in Neurodegeneration.

Deubiquitinases in Neurodegeneration.
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DOI:
10.3390/cells11030556
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发表时间:
2022-02-05
期刊:
影响因子:
6
通讯作者:
Mohan RD
Mohan RD
中科院分区:
生物学2区
文献类型:
--
作者:
Bello AI;Goswami R;Brown SL;Costanzo K;Shores T;Allan S;Odah R;Mohan RD

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泛素化是指泛素蛋白(一种在真核生物中高度保守的小蛋白)通过不同的使用泛素的七个内部连接位点或氨基末端氨基与自身或其他蛋白质结合。通过创造不同的链长,可能会形成巨大的蛋白质组多样性。这创造了一个信号系统,它是控制几乎所有可以想象到的蛋白质功能的中心,从蛋白平衡到调节酶功能以及介于两者之间的一切。蛋白质的泛素化通过去泛素酶(DUBS)的活性逆转,去泛素酶的功能是从自身和蛋白质底物中去结合泛素。DUBS通过几种机制进行调控,从细胞内受控的亚细胞定位到发育和组织特异性表达。DUBS的错误调控被认为与包括癌症和神经变性在内的几种疾病有关。在这里,我们简要概述DUBS在神经退行性变中的作用,以及作为潜在的治疗靶点。
Ubiquitination refers to the conjugation of the ubiquitin protein (a small protein highly conserved among eukaryotes) to itself or to other proteins through differential use of ubiquitin’s seven internal linkage sites or the amino-terminal amino group. By creating different chain lengths, an enormous proteomic diversity may be formed. This creates a signaling system that is central to controlling almost every conceivable protein function, from proteostasis to regulating enzyme function and everything in between. Protein ubiquitination is reversed through the activity of deubiquitinases (DUBs), enzymes that function to deconjugate ubiquitin from itself and protein substrates. DUBs are regulated through several mechanisms, from controlled subcellular localization within cells to developmental and tissue specific expression. Misregulation of DUBs has been implicated in several diseases including cancer and neurodegeneration. Here we present a brief overview of the role of DUBs in neurodegeneration, and as potential therapeutic targets.
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