Related Experiment Video

Updated: May 16, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

CKIP-1 inhibits cardiac hypertrophy by regulating class II histone deacetylase phosphorylation through recruiting

Shukuan Ling1, Qiao Sun, Yuheng Li

  • 1State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Haidian District, Beiqing Rd, Beijing, China.

Circulation
|November 16, 2012
PubMed
Abstract

Insights

Casein kinase-2 interacting protein-1 (CKIP-1) inhibits cardiac hypertrophy. CKIP-1 deficiency exacerbates heart enlargement, while its overexpression protects against it by regulating HDAC4 dephosphorylation.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Gene Regulation

Background:

  • Cardiac hypertrophy and remodeling are precursors to heart failure.
  • Casein kinase-2 interacting protein-1 (CKIP-1) is implicated in cell growth and death.
  • The role of CKIP-1 in cardiac physiology was previously undefined.

Purpose of the Study:

  • To investigate the physiological function of CKIP-1 in the heart.
  • To determine CKIP-1's role in cardiac hypertrophy and pathological remodeling.

Main Methods:

  • Echocardiography and histology in CKIP-1 deficient and transgenic mice.
  • GST pull-down and coimmunoprecipitation assays.
  • Analysis of protein-protein interactions and enzymatic activity.

Main Results:

  • CKIP-1 deficient mice showed spontaneous cardiac hypertrophy and hypersensitivity to pressure overload.
  • Overexpression of CKIP-1 conferred resistance to pressure overload-induced cardiac hypertrophy.
  • CKIP-1 interacts with Histone Deacetylase 4 (HDAC4), inhibiting its transcriptional activity and promoting its dephosphorylation via Phosphatase 2A.

Conclusions:

  • CKIP-1 acts as a crucial inhibitor of cardiac hypertrophy.
  • CKIP-1 suppresses cardiac hypertrophy by enhancing HDAC4 dephosphorylation through Protein Phosphatase 2A recruitment.
  • CKIP-1 regulates fetal gene expression, offering a novel therapeutic target for heart failure.

More Related Videos

Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity08:00

Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity

Published on: July 10, 2019

Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells05:38

Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells

Published on: February 12, 2021

Related Concept Videos

Cellular Adaptation II: Hypertrophy01:26

Cellular Adaptation II: Hypertrophy

Hypertrophy is the increase in the size of individual cells, resulting in the enlargement of a tissue or organ. Unlike hyperplasia, which involves an increase in cell number, hypertrophy is characterized by an increase in cell volume. This process often occurs in response to higher functional demand or hormonal stimulation, leading to the production of more structural proteins and organelles, thereby enhancing the cells' work capacity.There are two primary types of hypertrophy: physiological...
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...