Inhibition of CDK1 activity by sumoylation.
Inhibition of CDK1 activity by sumoylation.
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通过sumoylation抑制CDK1活性。
DOI：
10.1016/j.bbrc.2016.08.051
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发表时间：
2016-09-16
影响因子：
3.1
通讯作者：
Vigodner M
中科院分区：
文献类型：
--
作者：
Xiao Y;Lucas B;Molcho E;Schiff T;Vigodner M
Sumoylation（小型泛素样修饰剂或相扑蛋白的共价修饰）与调节各种细胞事件有关，包括细胞周期进程。我们最近确定了有丝分裂和减数分裂的主要调节剂CDK1是体内和体外的SUMO靶标，这支持了越来越多的证据表明在细胞周期进程过程中Sumoylation和Sumoylation和磷酸化之间的近距离交流。但是，缺少有关Sumoylation对CDK1活性影响的任何数据。
在这项研究中，我们进行了一系列体外实验，通过三种不同方法（银酸，氧化应激的生理水平以及使用siRNA方法）抑制Sumoylation，并使用特定的抗体和激酶测定法评估了CDK1活性的变化。除了评估抑制sumoylation时，我们还测试了SUMO与活性CDK1同工型之间的相互作用。我们的数据表明，抑制sumoylation可能通过变化sumoylated状态和/或特定蛋白质结合CDK1并抑制其活性的能力来增加CDK1的活性。
Sumoylation (a covalent modification by Small Ubiquitin-like Modifiers or SUMO proteins) has been implicated in the regulation of various cellular events including cell cycle progression. We have recently identified CDK1, a master regulator of mitosis and meiosis, as a SUMO target both in vivo and in vitro, supporting growing evidence concerning a close cross talk between sumoylation and phosphorylation during cell cycle progression. However, any data regarding the effect of sumoylation upon CDK1 activity have been missing. In this study, we performed a series of in vitro experiments to inhibit sumoylation by three different means (ginkgolic acid, physiological levels of oxidative stress, and using an siRNA approach) and assessed the changes in CDK1 activity using specific antibodies and a kinase assay. We have also tested for an interaction between SUMO and active and/or inactive CDK1 isoforms in addition to having assessed the status of CDK1-interacting sumoylated proteins upon inhibition of sumoylation. Our data suggest that inhibition of sumoylation increases the activity of CDK1 probably through changes in sumoylated status and/or the ability of specific proteins to bind CDK1 and inhibit its activity.