Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.2.1.13 (
glyceraldehyde-3-phosphate dehydrogenase
)
6,511
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Glyceraldehyde-3-phosphate dehydrogenase interacts with proapoptotic kinase mst1 to promote cardiomyocyte apoptosis. 2352 7
