Document Detail


Glyceraldehyde-3-phosphate dehydrogenase interacts with proapoptotic kinase mst1 to promote cardiomyocyte apoptosis.
MedLine Citation:
PMID:  23527007     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mammalian sterile 20-like kinase 1 (Mst1) is a critical component of the Hippo signaling pathway, which regulates a variety of biological processes ranging from cell contact inhibition, organ size control, apoptosis and tumor suppression in mammals. Mst1 plays essential roles in the heart disease since its activation causes cardiomyocyte apoptosis and dilated cardiomyopathy. However, the mechanism underlying Mst1 activation in the heart remains unknown. In a yeast two-hybrid screen of a human heart cDNA library with Mst1 as bait, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified as an Mst1-interacting protein. The interaction of GAPDH with Mst1 was confirmed by co-immunoprecipitation in both co-transfected HEK293 cells and mouse heart homogenates, in which GAPDH interacted with the kinase domain of Mst1, whereas the C-terminal catalytic domain of GAPDH mediated its interaction with Mst1. Moreover, interaction of Mst1 with GAPDH caused a robust phosphorylation of GAPDH and markedly increased the Mst1 activity in cells. Chelerythrine, a potent inducer of apoptosis, substantially increased the nuclear translocation and interaction of GAPDH and Mst1 in cardiomyocytes. Overexpression of GAPDH significantly augmented the Mst1 mediated apoptosis, whereas knockdown of GAPDH markedly attenuated the Mst1 activation and cardiomyocyte apoptosis in response to either chelerythrine or hypoxia/reoxygenation. These findings reveal a novel function of GAPDH in Mst1 activation and cardiomyocyte apoptosis and suggest that disruption of GAPDH interaction with Mst1 may prevent apoptosis related heart diseases such as heart failure and ischemic heart disease.
Authors:
Bei You; Shengdong Huang; Qing Qin; Bing Yi; Yang Yuan; Zhiyun Xu; Jianxin Sun
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-03-20
Journal Detail:
Title:  PloS one     Volume:  8     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2013  
Date Detail:
Created Date:  2013-03-25     Completed Date:  2013-09-20     Revised Date:  2013-10-28    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e58697     Citation Subset:  IM    
Affiliation:
Institute of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology*
Cell Line
Gene Knockdown Techniques
Glyceraldehyde-3-Phosphate Dehydrogenases / antagonists & inhibitors,  genetics,  metabolism*
HEK293 Cells
Hepatocyte Growth Factor / genetics,  metabolism*
Humans
Mice
Mice, Inbred C57BL
Myocytes, Cardiac / cytology*,  enzymology*
Protein Interaction Domains and Motifs
Protein-Serine-Threonine Kinases / genetics,  metabolism*
Proto-Oncogene Proteins / genetics,  metabolism*
Rats
Two-Hybrid System Techniques
Grant Support
ID/Acronym/Agency:
R01 HL103869/HL/NHLBI NIH HHS; R01HL103869/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins; 0/macrophage stimulating protein; 67256-21-7/Hepatocyte Growth Factor; EC 1.2.1.-/Glyceraldehyde-3-Phosphate Dehydrogenases; EC 2.7.1.-/STK4 protein, human; EC 2.7.1.-/Stk4 protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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