Acetylation of cyclin-dependent kinase 5 is mediated by GCN5.
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.
Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749, Republic of Korea.
Juhyung
J
Lee
Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749, Republic of Korea.
Nuri
N
Yun
Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749, Republic of Korea.
Chiho
C
Kim
Department of Physiology and Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul 130-701, Republic of Korea.
Min-Young
MY
Song
Department of Physiology and Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul 130-701, Republic of Korea.
Kang-Sik
KS
Park
Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749, Republic of Korea. Electronic address: yjoh@yonsei.ac.kr.
Young J
YJ
Oh
D000107:Acetylation; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D057809:HEK293 Cells; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
D051360:Cyclin-Dependent Kinase 5; D051548:Histone Acetyltransferases; D008239:Lysine; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
ATP; Acetylation; CDK5; GCN5; K33