title: Cyclin-dependent kinase-9 is a component of the p300/GATA4 complex required for phenylephrine-induced hypertrophy in cardiomyocytes.
abstract: A zinc finger protein GATA4 is one of the hypertrophy-responsive transcription factors and forms a complex with an intrinsic histone acetyltransferase, p300. Disruption of this complex results in the inhibition of cardiomyocyte hypertrophy and heart failure in vivo. By tandem affinity purification and mass spectrometric analyses, we identified cyclin-dependent kinase-9 (Cdk9) as a novel GATA4-binding partner. Cdk9 also formed a complex with p300 as well as GATA4 and cyclin T1. We showed that p300 was required for the interaction of GATA4 with Cdk9 and for the kinase activity of Cdk9. Conversely, Cdk9 kinase activity was required for the p300-induced transcriptional activities, DNA binding, and acetylation of GATA4. Furthermore, the kinase activity of Cdk9 was required for the phosphorylation of p300 as well as for cardiomyocyte hypertrophy. These findings demonstrate that Cdk9 forms a functional complex with the p300/GATA4 and is required for p300/GATA4- transcriptional pathway during cardiomyocyte hypertrophy.
authors.affiliation: Division of Translational Research, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sunagawa
authors.affiliation: Division of Translational Research, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555. Electronic address: mori@kuhp.kyoto-u.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Morimoto
authors.affiliation: Division of Translational Research, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555; Department of Cardiovascular Medicine, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Takaya
authors.affiliation: Division of Translational Research, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555; Department of Pediatrics, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kaichi
authors.affiliation: Division of Translational Research, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Wada
authors.affiliation: Division of Translational Research, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555.
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Kawamura
authors.affiliation: Human Health Sciences, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimatsu
authors.affiliation: Department of Cardiovascular Medicine, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.affiliation: Division of Translational Research, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555.
authors.forename: Koji
authors.initials: K
authors.lastname: Hasegawa
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010656:Phenylephrine / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; C084365:Gata4 protein, rat; D006657:Histones; D010656:Phenylephrine; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; C494362:Ep300 protein, rat; D042863:Cyclin-Dependent Kinase 9