Acetylation of cyclin-dependent kinase 5 is mediated by GCN5
Acetylation of cyclin-dependent kinase 5 is mediated by GCN5
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DOI：
10.1016/j.bbrc.2014.03.118
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发表时间：
2014-04-25
影响因子：
3.1
通讯作者：
Oh, Young J.
中科院分区：
文献类型：
--
作者：
Lee, Juhyung;Yun, Nuri;Oh, Young J.
细胞周期蛋白依赖性激酶5 （CDK5）是非典型丝氨酸/苏氨酸细胞周期蛋白依赖性激酶家族的成员，在神经退行性疾病的病理生理中起着至关重要的作用。它的激酶活性和底物特异性受几种独立途径的调节，包括与其激活剂的结合、磷酸化和s -亚硝基化。在本研究中，我们报告了CDK5的乙酰化包括细胞内额外的翻译后修饰。在众多候选物中，我们证实其乙酰化被GCN5增强，GCN5是组蛋白乙酰转移酶n -乙酰转移酶家族的一员。免疫共沉淀法和荧光定位研究表明，GCN5与CDK5物理相互作用，并在特定的核病灶上共定位。此外，液相色谱和质谱分析表明，CDK5在ATP结合域的Lys33残基上发生乙酰化。考虑到该赖氨酸位点在广泛的物种和其他相关的周期蛋白依赖激酶中是保守的，因此，我们推测乙酰化可能通过影响ATP协调的功效来改变CDK5的激酶活性。(c) 2014 Elsevier Inc.版权所有。
Cyclin-dependent kinase 5 (CDK5), a member of atypical serine/threonine cyclin-dependent kinase family, plays a crucial role in pathophysiology of neurodegenerative disorders. Its kinase activity and substrate specificity are regulated by several independent pathways including binding with its activator, phosphorylation and S-nitrosylation. In the present study, we report that acetylation of CDK5 comprises an additional posttranslational modification within the cells. Among many candidates, we confirmed that its acetylation is enhanced by GCN5, a member of the GCN5-related N-acetyl-transferase family of histone acetyltransferase. Co-immunoprecipitation assay and fluorescent localization study indicated that GCN5 physically interacts with CDK5 and they are co-localized at the specific nuclear foci. Furthermore, liquid chromatography in conjunction with a mass spectrometry indicated that CDK5 is acetylated at Lys33 residue of ATP binding domain. Considering this lysine site is conserved among a wide range of species and other related cyclin-dependent kinases, therefore, we speculate that acetylation may alter the kinase activity of CDK5 via affecting efficacy of ATP coordination. (c) 2014 Elsevier Inc. All rights reserved.