Protein-L-isoaspartate (D-aspartate) O-methyltransferase protects cardiomyocytes against hypoxia induced apoptosis through inhibiting proapoptotic kinase Mst1.
Protein-L-isoaspartate (D-aspartate) O-methyltransferase protects cardiomyocytes against hypoxia induced apoptosis through inhibiting proapoptotic kinase Mst1.
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蛋白-L-异天冬氨酸（D-天冬氨酸）O-甲基转移酶通过抑制促凋亡激酶 Mst1 保护心肌细胞免受缺氧诱导的细胞凋亡。
DOI：
10.1016/j.ijcard.2013.04.045
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发表时间：
2013-10-09
影响因子：
3.5
通讯作者：
Sun, Jianxin
中科院分区：
文献类型：
--
作者：
Yan, Guijun;Qin, Qing;Yi, Bing;Chuprun, Kurt;Sun, Haixiang;Huang, Shengdong;Sun, Jianxin
Mammalian sterile 20-like kinase 1 (Mst1) is a mammalian homolog of Hippo kinase from Drosophila and it 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 is not known. To identify novel cardiac proteins that may regulate Mst1 activity in the heart under pathophysiological conditions, a yeast two-hybrid screen of a human heart cDNA library with a dominant-negative Mst1 (K59R) mutant used as bait was performed. As a result, protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) was identified as an Mst1-interacting protein. The interaction of PCMT1 with Mst1 was confirmed by co-immunoprecipitation in both co-transfected HEK293 cells and native cardiomyocytes, in which PCMT1 interacted with the kinase domain of Mst1, but not with its C-terminal regulatory domain. Overexpression of PCMT1 did not affect the Mst1 expression, but significantly attenuated the Mst1 activation and its apoptotic effects in response to the hypoxia/reoxygenation induced injury in cardiomyocytes. Indeed, upregulation of PCMT1 by CGP3466B, a compound related to the anti-Parkinson’s drug R-(−)-deprenyl with potent antiapoptotic effects, inhibited the hypoxia/reoxygenation induced Mst1 activation and cardiomyocte apoptosis. These findings implicate PCMT1 as a novel inhibitor of Mst1 activation in cardiomyocytes and suggest that targeting PCMT1 may prevent myocardial apoptosis through inhibition of Mst1.
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影响因子：
4.8
作者：
Creasy, CL;Ambrose, DM;Chernoff, J
通讯作者：
Chernoff, J
影响因子：
3.5
作者：
Huebscher, KJ;Lee, J;Fürst, P
通讯作者：
Fürst, P
影响因子：
3.7
作者：
Cimmino A;Capasso R;Muller F;Sambri I;Masella L;Raimo M;De Bonis ML;D'Angelo S;Zappia V;Galletti P;Ingrosso D
通讯作者：
Ingrosso D
DOI：
10.1073/pnas.93.17.8977
发表时间：
1996-08-20
影响因子：
11.1
作者：
Lu, ML;Sato, M;Richie, JP
通讯作者：
Richie, JP
影响因子：
8
作者：
Chan, EH;Nousiainen, M;Silljé, HHW
通讯作者：
Silljé, HHW