The Emerging Roles of Protein Interactions with O-GlcNAc Cycling Enzymes in Cancer.
The Emerging Roles of Protein Interactions with O-GlcNAc Cycling Enzymes in Cancer.
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作者：
动态O-GlcNAc修饰在广泛的细胞过程中调节蛋白质的功能。负责O-GlcNAc循环的唯一酶O-GlcNAc转移酶（OGT）和O-GlcNAc酶（OGA）以及相关细胞O-GlcNAc谱的失调是几乎所有癌症类型的共同特征。在这里，我们强调了最近的研究OGT和OGA的结构特征，以及新出现的作用和分子机制的异常蛋白质-蛋白质相互作用（PPI）在重新布线癌症网络，以帮助确定关键的蛋白质接触和功能模块，推动恶性肿瘤和促进癌症治疗创新。细胞内蛋白质的动态O-GlcNAc修饰是将代谢信号整合到高度协调的细胞活动的巨大网络中的重要营养传感器。负责O-GlcNAc循环的唯一酶O-GlcNAc转移酶（OGT）和O-GlcNAc酶（OGA）以及相关细胞O-GlcNAc谱的失调是几乎所有癌症类型的共同特征。许多研究已经调查了异常OGT/OGA表达对癌细胞中总体O-GlcNAc化活性的影响。然而，最近的研究已经开始阐明蛋白质-蛋白质相互作用（PPIs）的作用，可能通过OGT/OGA的直接催化位点以外的区域，调节更大的蛋白质网络，以促进底物特异性修饰，蛋白质易位，以及更大的生物分子复合物的组装。OGT/OGA PPI网络的扰动使细胞发生深刻变化，并可能直接导致癌症恶性肿瘤。在此，我们强调了最近的研究OGT和OGA的结构特征，以及新兴的作用和分子机制的异常PPI在重新布线癌症网络。通过整合互补方法，这一领域的研究将有助于识别来自OGT/OGA的关键蛋白质接触和功能模块，这些模块驱动肿瘤发生，并将为抗癌药物开发指明新的方向。
Dynamic O-GlcNAc modification regulates the functions of proteins in a broad range of cellular processes. Dysregulation of the sole enzymes responsible for O-GlcNAc cycling, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), and the associated cellular O-GlcNAc profile is a common feature across nearly every cancer type. Here, we highlight recent studies on the structural features of OGT and OGA, as well as the emerging roles and molecular mechanisms of their aberrant protein–protein interactions (PPIs) in rewiring cancer networks, to help identify key protein contacts and functional modules that drive malignancies and to promote cancer therapeutic innovations. The dynamic O-GlcNAc modification of intracellular proteins is an important nutrient sensor for integrating metabolic signals into vast networks of highly coordinated cellular activities. Dysregulation of the sole enzymes responsible for O-GlcNAc cycling, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), and the associated cellular O-GlcNAc profile is a common feature across nearly every cancer type. Many studies have investigated the effects of aberrant OGT/OGA expression on global O-GlcNAcylation activity in cancer cells. However, recent studies have begun to elucidate the roles of protein–protein interactions (PPIs), potentially through regions outside of the immediate catalytic site of OGT/OGA, that regulate greater protein networks to facilitate substrate-specific modification, protein translocalization, and the assembly of larger biomolecular complexes. Perturbation of OGT/OGA PPI networks makes profound changes in the cell and may directly contribute to cancer malignancies. Herein, we highlight recent studies on the structural features of OGT and OGA, as well as the emerging roles and molecular mechanisms of their aberrant PPIs in rewiring cancer networks. By integrating complementary approaches, the research in this area will aid in the identification of key protein contacts and functional modules derived from OGT/OGA that drive oncogenesis and will illuminate new directions for anti-cancer drug development.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1083/jcb.201501101
发表时间：
2015-03-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bond MR;Hanover JA
通讯作者：
Hanover JA
通过人类蛋白质组微阵列全面鉴定 O-GlcNAc 转移酶 (OGT) 相互作用因子并构建 OGT 相互作用组
影响因子：
3.4
作者：
Deng, Rui-Ping;He, Xiang;Tao, Sheng-Ce
通讯作者：
Tao, Sheng-Ce
影响因子：
16.8
作者：
Dennis, RJ;Taylor, EJ;Davies, GJ
通讯作者：
Davies, GJ
影响因子：
30.8
作者：
Cheng F;Zhao J;Wang Y;Lu W;Liu Z;Zhou Y;Martin WR;Wang R;Huang J;Hao T;Yue H;Ma J;Hou Y;Castrillon JA;Fang J;Lathia JD;Keri RA;Lightstone FC;Antman EM;Rabadan R;Hill DE;Eng C;Vidal M;Loscalzo J
通讯作者：
Loscalzo J