Acetylation of cyclin-dependent kinase 5 is mediated by GCN5

Journal Article · Fri Apr 25 04:00:00 EDT 2014 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2014.03.118· OSTI ID:22416402

Lee, Juhyung; Yun, Nuri; Kim, Chiho ^[1]; Song, Min-Young; Park, Kang-Sik ^[2]

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1. Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of)
2. Department of Physiology and Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul 130-701 (Korea, Republic of)

Highlights: • Cyclin-dependent kinase 5 (CDK5) is present as an acetylated form. • CDK5 is acetylated by GCN5. • CDK5’s acetylation site is mapped at Lys33. • Its acetylation may affect CDK5’s kinase activity. - 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.

• OSTI ID: 22416402
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 447; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACETYLATION
ATP
FLUORESCENCE
LIQUID COLUMN CHROMATOGRAPHY
LYSINE
MASS SPECTROSCOPY
PHOSPHORYLATION
PHOSPHOTRANSFERASES
RESIDUES
SERINE
SPECIFICITY
SUBSTRATES
THREONINE