Network Analysis of UBE3A/E6AP-Associated Proteins Provides Connections to Several Distinct Cellular Processes.
Network Analysis of UBE3A/E6AP-Associated Proteins Provides Connections to Several Distinct Cellular Processes.
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DOI：
10.1016/j.jmb.2018.01.021
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发表时间：
2018-03-30
影响因子：
5.6
通讯作者：
Howley PM
中科院分区：
文献类型：
--
作者：
Martínez-Noël G;Luck K;Kühnle S;Desbuleux A;Szajner P;Galligan JT;Rodriguez D;Zheng L;Boyland K;Leclere F;Zhong Q;Hill DE;Vidal M;Howley PM
UBE3A泛素连接酶的活性和剂量的扰动与Angelman综合征和自闭症谱系障碍有关。UBE3A最初被确定为被人乳头瘤病毒E6蛋白劫持的细胞蛋白，介导p53的泛素化，这是这些病毒致癌潜力的关键功能。虽然已经确定了许多底物，但UBE3A影响的正常细胞功能和途径在很大程度上是未知的。在此之前，我们发现UBE3A与HERC2、NEURL4和MAPK6/ERK3结合在一个高分子量复合物中，其功能未知，我们称之为HUN复合物（HERC2、UBE3A和NEURL4）。在这项研究中，两种互补的蛋白质组学方法结合严格的网络分析揭示了UBE3A和HUN复合物参与的细胞功能和途径。除了发现新的UBE3A相关蛋白，如MCM6、SUGT1、EIF3C和ASPP2，网络分析还揭示了UBE3A相关蛋白与几个基本的细胞过程有关，包括翻译、DNA复制、细胞内运输和中心体调节。我们的分析表明，UBE3A可能参与这些细胞过程的控制和/或整合，在某些情况下作为HUN复合体的一个组成部分，并且也为HUN复合体和CAMKII相互作用网络之间的串扰提供了证据。这项研究有助于更深入地了解UBE3A的细胞功能及其在Angelman综合征、UBE3A相关自闭症谱系障碍和hpv相关癌症中可能受影响的途径中的潜在作用。
Perturbations in activity and dosage of the UBE3A ubiquitin-ligase have been linked to Angelman Syndrome and autism spectrum disorders. UBE3A was initially identified as the cellular protein hijacked by the human papillomavirus E6 protein to mediate the ubiquitylation of p53, a function critical to the oncogenic potential of these viruses. Although a number of substrates have been identified, the normal cellular functions and pathways affected by UBE3A are largely unknown. Previously we showed that UBE3A associates with HERC2, NEURL4, and MAPK6/ERK3 in a high molecular weight complex of unknown function that we refer to as the HUN complex (HERC2, UBE3A, and NEURL4). In this study, the combination of two complementary proteomic approaches with a rigorous network analysis revealed cellular functions and pathways in which UBE3A and the HUN complex are involved. In addition to finding new UBE3A-associated proteins, such as MCM6, SUGT1, EIF3C, and ASPP2, network analysis revealed that UBE3A associated proteins are connected to several fundamental cellular processes including translation, DNA replication, intracellular trafficking, and centrosome regulation. Our analysis suggests that UBE3A could be involved in the control and/or integration of these cellular processes, in some cases as a component of the HUN complex, and also provides evidence for crosstalk between the HUN complex and CAMKII interaction networks. This study contributes to a deeper understanding of the cellular functions of UBE3A and its potential role in pathways that may be affected in Angelman Syndrome, UBE3A-associated autism spectrum disorders and HPV-associated cancers.
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影响因子：
64.8
作者：
Bingol, Baris;Schuman, Erin M.
通讯作者：
Schuman, Erin M.
影响因子：
5.8
作者：
Berriz, GF;King, OD;Roth, FP
通讯作者：
Roth, FP
DOI：
10.1073/pnas.1217072110
发表时间：
2013-03-12
影响因子：
11.1
作者：
Britschgi, Adrian;Bill, Anke;Bentires-Alj, Mohamed
通讯作者：
Bentires-Alj, Mohamed
安丙定促进脊柱肌动蛋白聚合，长期增强和在Angelman综合征的小鼠模型中学习。
影响因子：
6.1
作者：
Baudry M;Kramar E;Xu X;Zadran H;Moreno S;Lynch G;Gall C;Bi X
通讯作者：
Bi X
影响因子：
5.2
作者：
Ben-Shushan, Etti;Feldman, Eva;Reubinoff, Benjamin E.
通讯作者：
Reubinoff, Benjamin E.