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Ubiquitin

内分泌

关键词内分泌 临床研究术语 蛋白

词汇介绍

拓展阅读

解析

Ubiquitin   英/ju:'bikwitin/

释    义   n. 泛激素,泛素

例    句   Scientists had shown previously that DNA repair was much less efficient when FANCI and FANCD2 lack the single ubiquitin.在此之前,科学家就已清楚,在FANCI和FANCD2缺少单泛素时,DNA修复基本无效。

概述

泛素是在真核生物的大多数组织中发现的普遍存在的一种小的(8.6 kDa)调节蛋白。它是由吉迪恩·戈德斯坦(Gideon Goldstein)于1975年发现的,并在整个1970年代和1980年代得到了进一步的表征。人类基因组中的四个基因编码泛素,分别是:UBB,UBC,UBA52和RPS27A。 类型 泛素化通过调节蛋白质降解(通过蛋白酶体和溶酶体),协调蛋白质在细胞中的定位,激活和失活蛋白质以及调节蛋白质-蛋白质相互作用来影

Heat Shock Protein 90 Chaperone Regulates the E3 Ubiquitin-Ligase Hakai Protein Stability复制标题

热休克蛋白90伴侣调控E3泛素连接酶Hakai蛋白稳定性

发表时间:2020-02-15

影响因子:6.2

作者: Andrea Díaz-Díaz

期刊:Cancers (Basel)

Hakai is a new class of the three families of RING-finger type E3 ubiquitin-ligases that contains a novel domain called HYB (Hakai pTyr-binding) whereby it interacts with the tyrosinephosphorylated substrates inducing their ubiquitination and degradation. So far, the best characterized substrate for Hakai is E-cadherin. Hakai interacts with the Src tyrosine-phosphorylated E-cadherin, inducing its ubiquitination and degradation, which in turn causes the alteration of cell- cell contacts. E-cadherin is the best-characterized member of the adherens junctions and its loss at cell-cell adhesions is a well stablished hallmark of the epithelial-to-mesenchymal transition during tumor progression and metastasis. Hakai is not only involved in the regulation of cell– cell adhesions but also in regulating cell proliferation, cell motility and invasion. Importantly, Hakai is highly expressed in colon and lung cancer compared to human healthy tissues. Additional target proteins for Hakai, such as Cortactin or DOK1, have been identified, however, the functional significance is still unknown. Recently, we employed an iTRAQ approach and found differentially regulated proteins in epithelial MDCK cell lines stably expressing Hakai compared to non-transformed MDCK cells. Interestingly, several membrane-binding proteins, including Annexin A2, were confirmed to be decreased in Hakai-overexpressing cells while other proteins, such as Hsp90 chaperone, were slightly increased.

译文

Hakai是无名指E3型泛素连接酶的三个家族中的一个新分类,它包含一个新的结构域HYB(Hakai-pTyr-binding),通过它与酪氨酸磷酸化底物相互作用,诱导其泛素化和降解。迄今为止,Hakai的最佳特征底物是E-钙粘蛋白。Hakai与Src酪氨酸磷酸化E-钙粘蛋白相互作用,诱导其泛素化和降解,进而引起细胞-细胞接触的改变。E-cadherin是粘附连接中最具特征性的成员,其在细胞粘附时的丢失是肿瘤进展和转移过程中上皮向间质转化的一个很好的标志。Hakai不仅参与细胞粘附的调节,而且参与细胞增殖、细胞运动和侵袭的调节。重要的是,与人类健康组织相比,Hakai在结肠癌和肺癌中高表达。客家人的其他靶蛋白,如皮质素或DOK1,已经被鉴定,但其功能意义尚不清楚。最近,我们采用iTRAQ方法,在稳定表达Hakai的上皮MDCK细胞系中发现了与未转化MDCK细胞相比的差异调节蛋白。有趣的是,一些膜结合蛋白,包括膜联蛋白A2,被证实在Hakai过表达细胞中减少,而其他蛋白质,如HSP90伴侣,略有增加。