title: CKIP-1 inhibits cardiac hypertrophy by regulating class II histone deacetylase phosphorylation through recruiting PP2A.
abstract: BACKGROUND
  Sustained cardiac pressure overload-induced hypertrophy and pathological remodeling frequently leads to heart failure. Casein kinase-2 interacting protein-1 (CKIP-1) has been identified to be an important regulator of cell proliferation, differentiation, and apoptosis. However, the physiological role of CKIP-1 in the heart is unknown.
  
  
  RESULTS
  The results of echocardiography and histology demonstrate that CKIP-1-deficient mice exhibit spontaneous cardiac hypertrophy with aging and hypersensitivity to pressure overload-induced pathological cardiac hypertrophy, as well. Transgenic mice with cardiac-specific overexpression of CKIP-1 showed resistance to cardiac hypertrophy in response to pressure overload. The results of GST pull-down and coimmunoprecipitation assays showed the interaction between CKIP-1 and histone deacetylase 4 (HDAC4), through which they synergistically inhibited transcriptional activity of myocyte-specific enhancer factor 2C. By directly interacting with the catalytic subunit of phosphatase 2A, CKIP-1 overexpression enhanced the binding of catalytic subunit of phosphatase-2A to HDAC4 and promoted HDAC4 dephosphorylation.
  
  
  CONCLUSIONS
  CKIP-1 was found to be an inhibitor of cardiac hypertrophy by upregulating the dephosphorylation of HDAC4 through the recruitment of protein phosphatase 2A. These results demonstrated a unique function of CKIP-1, by which it suppresses cardiac hypertrophy through its capacity to regulate HDAC4 dephosphorylation and fetal cardiac genes expression.
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Haidian District, Beiqing Rd, Beijing, China.
authors.forename: Shukuan
authors.initials: S
authors.lastname: Ling
authors.forename: Qiao
authors.initials: Q
authors.lastname: Sun
authors.forename: Yuheng
authors.initials: Y
authors.lastname: Li
authors.forename: Luo
authors.initials: L
authors.lastname: Zhang
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhang
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Wang
authors.forename: Chunyan
authors.initials: C
authors.lastname: Tian
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Jinping
authors.initials: J
authors.lastname: Song
authors.forename: Hongju
authors.initials: H
authors.lastname: Liu
authors.forename: Guanghan
authors.initials: G
authors.lastname: Kan
authors.forename: Hongqing
authors.initials: H
authors.lastname: Cao
authors.forename: Zengming
authors.initials: Z
authors.lastname: Huang
authors.forename: Jielin
authors.initials: J
authors.lastname: Nie
authors.forename: Yanqiang
authors.initials: Y
authors.lastname: Bai
authors.forename: Shanguang
authors.initials: S
authors.lastname: Chen
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Li
mesh_terms: D000367:Age Factors; D000818:Animals; D006332:Cardiomegaly / Q000517:prevention & control*; D002352:Carrier Proteins / Q000502:physiology*; D006655:Histone Deacetylases / Q000502:physiology*; D064326:MEF2 Transcription Factors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000502:physiology; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000502:physiology*; D014158:Transcription, Genetic; D047908:Intracellular Signaling Peptides and Proteins
chemical_list: D002352:Carrier Proteins; D006655:Histone Deacetylases; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D054648:Protein Phosphatase 2; C578041:Mef2c protein, mouse; C498618:Hdac5 protein, mouse; C000620556:PLEKHO1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins