Document Detail


CKIP-1 Inhibits Cardiac Hypertrophy by Regulating Class II Histone Deacetylase Phosphorylation through Recruiting PP2A.
MedLine Citation:
PMID:  23151343     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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. METHODS AND RESULTS: The results of echocardiography and histology demonstrated that CKIP-1-deficient mice exhibit spontaneous cardiac hypertrophy with aging as well as hypersensitivity to pressure overload-induced pathological cardiac hypertrophy. Transgenic mice with cardiac-specific over-expression of CKIP-1 showed resistance to cardiac hypertrophy in response to pressure overload. The results of GST pull down and Co-immunoprecipitation assays showed the interaction between CKIP-1 and HDAC4, through which they synergistically inhibited transcriptional activity of MEF2C. By directly interacting with the catalytic subunit of phosphatase-2A (PP2AC), CKIP-1 over-expression enhanced the binding of PP2AC to HDAC4 and promoted HDAC4 dephosphorylation. CONCLUSIONS: CKIP-1 was found to be an inhibitor of cardiac hypertrophy by up-regulating the dephosphorylation of HDAC4 through the recruitment of PP2A. 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:
Shukuan Ling; Qiao Sun; Yuheng Li; Luo Zhang; Pengfei Zhang; Xiaogang Wang; Chunyan Tian; Qi Li; Jinping Song; Hongju Liu; Guanghan Kan; Hongqing Cao; Zengming Huang; Jielin Nie; Yanqiang Bai; Shanguang Chen; Yinghui Li; Fuchu He; Lingqiang Zhang; Yingxian Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-14
Journal Detail:
Title:  Circulation     Volume:  -     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 China Astronaut Research and Training Center, Beijing, China;
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