Regulation of proteolysis by human deubiquitinating enzymes.
Regulation of proteolysis by human deubiquitinating enzymes.
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DOI：
10.1016/j.bbamcr.2013.06.027
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发表时间：
2014-01
影响因子：
5.1
通讯作者：
Wilkinson, Keith D.
中科院分区：
文献类型：
--
作者：
Eletr, Ziad M.;Wilkinson, Keith D.
一个或几个泛素分子与蛋白质的翻译后连接产生了多种靶向信号，这些信号在细胞中以许多不同的方式使用。泛素化可以改变靶蛋白的活性、定位、蛋白质-蛋白质相互作用或稳定性。此外，大量的蛋白质受到泛素依赖性过程的调节，这意味着几乎所有的细胞功能都受到这些途径的影响。来自5个不同基因家族的近100种酶（去泛素化酶或DUBs）通过水解将泛素连接到自身或靶蛋白上的（异）肽键来逆转这种修饰。这些家族中的四个是巯基蛋白酶，一个是金属蛋白酶。泛素C末端水解酶（UCH）家族的DUB作用于泛素的小分子加合物，加工泛素前蛋白，并从多聚泛素链的远端修剪泛素。泛素特异性蛋白酶（USP）倾向于通过其序列的可变区与底物蛋白直接相互作用或与多蛋白复合物中的支架或底物衔接子相互作用来识别和遇到其底物。卵巢肿瘤（OTU）结构域DUB对不同的Ub链连接显示出显著的特异性，并且可能已经进化为基于这些连接识别底物。DUB的Josephin家族可能专门区分不同长度的聚泛素链。最后，JAB 1/MPN+/MOV 34（JAMM）结构域金属蛋白酶切割聚泛素和底物的连接点附近的异肽键，并且对K63聚Ub连接具有高度特异性。这些DUB通过以下方式调节蛋白水解：直接与E3连接酶相互作用并共调节E3连接酶;改变底物泛素化水平;水解或重塑泛素化和多聚泛素化底物;作用于细胞中的特定位置并改变靶蛋白的定位;以及作用于蛋白酶体结合底物以促进或抑制蛋白水解。因此，泛素途径的范围和调节与磷酸化非常相似，DUB与磷酸酶具有相同的功能。
The post-translational attachment of one or several ubiquitin molecules to a protein generates a variety of targeting signals that are used in many different ways in the cell. Ubiquitination can alter the activity, localization, protein-protein interactions or stability of the targeted protein. Further, a very large number of proteins are subject to regulation by ubiquitin-dependent processes, meaning that virtually all cellular functions are impacted by these pathways. Nearly a hundred enzymes from five different gene families (the deubiquitinating enzymes or DUBs), reverse this modification by hydrolyzing the (iso)peptide bond tethering ubiquitin to itself or the target protein. Four of these families are thiol proteases and one is a metalloprotease. DUBs of the Ubiquitin C-terminal Hydrolase (UCH) family act on small molecule adducts of ubiquitin, process the ubiquitin proprotein, and trim ubiquitin from the distal end of a polyubiquitin chain. Ubiquitin Specific Proteases (USP) tend to recognize and encounter their substrates by interaction of the variable regions of their sequence with the substrate protein directly, or with scaffolds or substrate adapters in multiprotein complexes. Ovarian Tumor (OTU) domain DUBs show remarkable specificity for different Ub chain linkages and may have evolved to recognize substrates on the basis of those linkages. The Josephin family of DUBs may specialize in distinguishing between polyubiquitin chains of different lengths. Finally, the JAB1/MPN+/MOV34 (JAMM) domain metalloproteases cleave the isopeptide bond near the attachment point of polyubiquitin and substrate, as well as being highly specific for the K63 poly-Ub linkage. These DUBs regulate proteolysis by: directly interacting with and co-regulating E3 ligases; altering the level of substrate ubiquitination; hydrolyzing or remodeling ubiquitinated and poly-ubiquitinated substrates; acting in specific locations in the cell and altering the localization of the target protein; and acting on proteasome bound substrates to facilitate or inhibit proteolysis. Thus, the scope and regulation of the ubiquitin pathway is very similar to that of phosphorylation, with the DUBs serving the same functions as the phosphatase.
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影响因子：
3.5
作者：
Atanassov BS;Koutelou E;Dent SY
通讯作者：
Dent SY
影响因子：
50.3
作者：
Abdel-Wahab O;Adli M;LaFave LM;Gao J;Hricik T;Shih AH;Pandey S;Patel JP;Chung YR;Koche R;Perna F;Zhao X;Taylor JE;Park CY;Carroll M;Melnick A;Nimer SD;Jaffe JD;Aifantis I;Bernstein BE;Levine RL
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影响因子：
16
作者：
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通讯作者：
Dick, Lawrence R.
影响因子：
11.4
作者：
Cooper, Eric M.;Cutcliffe, Colleen;Cohen, Robert E.
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影响因子：
4.8
作者：
Choi, J;Levey, AI;Li, L
通讯作者：
Li, L