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Cyclin-dependent kinase-9 is a component of the p300/GATA4 complex required for phenylephrine-induced hypertrophy in

Yoichi Sunagawa1, Tatsuya Morimoto1, Tomohide Takaya2

  • 1Division of Translational Research, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555.

The Journal of Biological Chemistry
|January 19, 2010
PubMed

Insights

Cyclin-dependent kinase-9 (Cdk9) interacts with GATA4 and p300, regulating cardiomyocyte hypertrophy. Cdk9 kinase activity is essential for GATA4 acetylation and p300 phosphorylation, crucial for heart function.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Epigenetics

Background:

  • GATA4, a transcription factor, interacts with p300, a histone acetyltransferase, and is vital for cardiomyocyte hypertrophy.
  • Disruption of the GATA4-p300 complex leads to heart failure.
  • Understanding the regulation of this complex is crucial for cardiac health.

Purpose of the Study:

  • To identify novel binding partners of GATA4.
  • To elucidate the role of new partners in the GATA4-p300 complex.
  • To investigate the functional significance of these interactions in cardiomyocyte hypertrophy.

Main Methods:

  • Tandem affinity purification
  • Mass spectrometry
  • Co-immunoprecipitation
  • In vivo studies of cardiomyocyte hypertrophy

Main Results:

  • Cyclin-dependent kinase-9 (Cdk9) was identified as a novel GATA4-binding partner.
  • Cdk9 forms a complex with GATA4, p300, and cyclin T1.
  • Cdk9 kinase activity is required for GATA4 acetylation, p300 phosphorylation, and cardiomyocyte hypertrophy.

Conclusions:

  • Cdk9 is a key component of the GATA4-p300 transcriptional complex.
  • Cdk9 kinase activity is essential for the GATA4-p300 pathway in cardiomyocyte hypertrophy.
  • Cdk9 represents a potential therapeutic target for heart failure.

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