Acetylation of cyclin-dependent kinase 5 is mediated by GCN5 |
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Authors: | Juhyung Lee Nuri Yun Chiho Kim Min-Young Song Kang-Sik Park Young J Oh |
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Institution: | 1. Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749, Republic of Korea;2. Department of Physiology and Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul 130-701, Republic of Korea |
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Abstract: | 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. |
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Keywords: | CDK5 GCN5 Acetylation K33 ATP |
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