SUMO2/3 modification of activating transcription factor 5 (ATF5) controls its dynamic translocation at the centrosome
SUMO2/3 modification of activating transcription factor 5 (ATF5) controls its dynamic translocation at the centrosome
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SUMO2/3 激活转录因子 5 (ATF5) 的修饰控制其在中心体的动态易位
DOI：
10.1074/jbc.ra117.001151
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发表时间：
2018-01
影响因子：
4.8
通讯作者：
Liu David X
中科院分区：
文献类型：
--
作者：
Yuan Yunsheng;Gaither Kari;Kim Eugene;Liu Edward;Hu Ming;Lengel Kathy;Qian Dongmeng;Xu Yidi;Wang Bin;Knipprath Henning;Liu David X
激活转录因子5(ATF5)是转录因子ATF/cAMP反应元件结合蛋白家族的成员。ATF5调节应激反应和细胞的存活、增殖和分化，也在病毒感染、癌症、糖尿病、精神分裂症和嗅觉系统中发挥作用。此外，它还被发现在中心体具有关键的细胞周期依赖的结构功能。然而，控制ATF5在中心体定位的机制尚不清楚。在这里，我们报道ATF5是一种小泛素样修饰物(SUMO)2/3-在各种类型的哺乳动物细胞中保守的相扑靶向共同位点进行修饰。我们发现ATF5的SUMO化在细胞周期的G1期升高，在G2/M期减弱。ATF5的SUMO化破坏了ATF5与几种中心体蛋白的相互作用，并在M期结束时将ATF5从中心体上移走。值得注意的是，阻断ATF5的SUMO化破坏了中心体周期，阻止了ATF5从中心体移位，并导致了基因组的不稳定和HeLa细胞的G2/M期停滞。我们的结果表明，ATF5的SUMO化是调节ATF5在中心体的定位和功能的重要机制。
Activating transcription factor 5 (ATF5) is a member of the ATF/cAMP response element–binding protein family of transcription factors. ATF5 regulates stress responses and cell survival, proliferation, and differentiation and also plays a role in viral infections, cancer, diabetes, schizophrenia, and the olfactory system. Moreover, it was found to also have a critical cell cycle–dependent structural function at the centrosome. However, the mechanism that controls the localization of ATF5 at the centrosome is unclear. Here we report that ATF5 is small ubiquitin-like modifier (SUMO) 2/3–modified at a conserved SUMO-targeting consensus site in various types of mammalian cells. We found that SUMOylation of ATF5 is elevated in the G1 phase of the cell cycle and diminished in the G2/M phase. ATF5 SUMOylation disrupted the interaction of ATF5 with several centrosomal proteins and dislodged ATF5 from the centrosome at the end of the M phase. Of note, blockade of ATF5 SUMOylation deregulated the centrosome cycle, impeded ATF5 translocation from the centrosome, and caused genomic instability and G2/M arrest in HeLa cells. Our results indicate that ATF5 SUMOylation is an essential mechanism that regulates ATF5 localization and function at the centrosome.
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影响因子：
7
作者：
Vertegaal, Alfred C. O.;Andersen, Jens S.;Lamond, Angus I.
通讯作者：
Lamond, Angus I.
DOI：
10.1158/1541-7786.mcr-08-0365
发表时间：
2009-06
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Li G;Li W;Angelastro JM;Greene LA;Liu DX
通讯作者：
Liu DX
DOI：
10.1523/jneurosci.23-11-04590.2003
发表时间：
2003-06
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
J. Angelastro;T. Ignatova;V. Kukekov;D. Steindler;George B Stengren;C. Mendelsohn;L. Greene
通讯作者：
J. Angelastro;T. Ignatova;V. Kukekov;D. Steindler;George B Stengren;C. Mendelsohn;L. Greene
影响因子：
10.5
作者：
Liang J;Singh N;Carlson CR;Albuquerque CP;Corbett KD;Zhou H
通讯作者：
Zhou H
干扰 ATF5 功能增强人胰腺癌细胞对紫杉醇诱导的细胞凋亡的敏感性
影响因子：
2
作者：
Hu, Ming;Wang, Bin;Qian, Dongmeng;Li, Ling;Zhang, Li;Song, Xuxia;Liu, David X.
通讯作者：
Liu, David X.