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Possible mechanism of GATA4 inhibiting myocardin activity during cardiac hypertrophy

Yao Xu1, Chen Liang1, Ying Luo1

  • 1Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, China.

Journal of Cellular Biochemistry
|December 25, 2018
PubMed

Insights

GATA4 inhibits myocardin activity in cardiac hypertrophy through competitive binding, reduced acetylation, and increased phosphorylation. These mechanisms clarify GATA4 and myocardin roles in heart disease development.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Myocardin is a key regulator of cardiac hypertrophy.
  • GATA4 influences myocardin activity, but the precise molecular mechanisms are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which GATA4 inhibits myocardin activity during cardiac hypertrophy.

Main Methods:

  • Investigated competitive binding of GATA4 and SRF to myocardin.
  • Assessed the effect of GATA4 on myocardin acetylation via p300 interaction.
  • Examined GATA4-mediated phosphorylation of myocardin upon ERK pathway activation.

Main Results:

  • GATA4 overexpression competitively binds SRF, reducing myocardin-SRF-CarG box complex formation.
  • GATA4 inhibits myocardin-p300 interaction, leading to decreased myocardin acetylation.
  • GATA4 upregulates myocardin phosphorylation through the ERK pathway.

Conclusions:

  • GATA4 employs multiple molecular strategies to inhibit myocardin activity in cardiac hypertrophy.
  • These findings enhance understanding of GATA4 and myocardin roles in cardiac hypertrophy pathogenesis.

Keywords:
GATA4cardiac hypertrophymyocardinsignaling pathway

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