USP8 – Another DUB in the T cell club
USP8 – Another DUB in the T cell club
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USP8 – T 细胞俱乐部中的另一个 DUB
DOI：
10.1080/15384101.2015.1105698
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发表时间：
2015
期刊：
影响因子：
4.3
通讯作者：
Knobeloch KP
中科院分区：
文献类型：
--
作者：
Dufner A;Knobeloch KP
泛素对蛋白质的修饰在多种细胞过程中起着关键作用，并被人类基因组编码的> 90种去泛素化酶（DUB）的活性所抵消。除了催化核心结构域之外，大多数DUB还含有各种蛋白质-蛋白质相互作用结构域，这些结构域决定底物特异性和多分子复合物的募集。然而，大多数哺乳动物DUB在特定细胞类型中的生理相关性仍然难以捉摸。1几种DUB，如A20、淋巴瘤病（CYLD）、USP 9 X和USP 15，被证明对适当的T细胞功能至关重要。2我们现在鉴定出泛素特异性蛋白酶8（USP 8）是T细胞受体（TCR）信号体的一种新组分，它与衔接分子Gads和调节蛋白14-3-3b相互作用。3 Gads在T细胞中高度丰富，并调节信号多样化。4作为14-3-3蛋白的典型特征，与14-3-3b的相互作用依赖于USP 8的14-3-3结合基序（14-3-3BM）内的丝氨酸磷酸化基序（图1）。在包括肝细胞、成纤维细胞和腺瘤细胞的几种细胞类型中，显示USP 8控制跨膜蛋白的内体分选。5，6通过介导货物底物和内体分选复合物（ESCRT）组分的去泛素化，USP 8抵消溶酶体降解，从而稳定受体酪氨酸激酶，如EGFR。5-7值得注意的是，与MEF和肝细胞相反，缺乏USP 8对内体分选组分的稳定性没有影响。
Protein modification by ubiquitin plays a critical role in multiple cellular processes and is counteracted by the activity of» 90 deubiquitinating enzymes (DUBs) encoded by the human genome. Beside the catalytic core domain most DUBs contain various protein-proteininteraction domains, which determine substrate specificity and recruitment to multi-molecular complexes. However, the physiological relevance of most mammalian DUBs in particular cell types remains elusive. 1Several DUBs like A20, Cylindromatosis (CYLD), USP9X, and USP15 were shown to be essential for proper T cell function. 2 We now identified ubiquitinspecific protease 8 (USP8) as a novel component of the T cell receptor (TCR) signalosome that interacts with the adapter molecule Gads and the regulatory protein 14–3–3b. 3 Gads is highly abundant in T cells and modulates signal diversification. 4 As typical for 14–3–3 proteins, the interaction with 14–3–3b was dependent on a serine phosphorylation motif within the 14–3–3 binding motif (14–3–3BM) of USP8 (Fig. 1). In several cell types including hepatocytes, fibroblasts and adenoma cells USP8 was shown to control endosomal sorting of transmembrane proteins. 5, 6 By mediating deubiquitination of cargo substrates and components of the endosomal sorting complex (ESCRT) USP8 counteracts lysosomal degradation and thus stabilizes receptor tyrosine kinases such as the EGFR. 5-7 Remarkably, in contrast to MEFs and hepatocytes, lack of USP8 had no influence on the stability of components of the endosomal sorting
影响因子：
30.5
作者：
Dufner, Almut;Kisser, Agnes;Knobeloch, Klaus-Peter
通讯作者：
Knobeloch, Klaus-Peter