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Pi3kcb Links Hippo-YAP and PI3K-AKT Signaling Pathways to Promote Cardiomyocyte Proliferation and Survival 期刊论文

编号：

8943ed2b-7445-41f2-bf1c-2fce23235851
作者：

Lin, Zhiqiang#^[1]Zhou, Pingzhu^[1];von Gise, Alexander^[1,2];Gu, Fei^[1];Ma, Qing^[1];Chen, Jinghai^[1];Guo, Haidong(国海东)^[1,3]van Gorp, Pim R. R.^[1,4];Wang, DaZhi^[1,5];Pu, William T.*^[1,5]
语种：

英文
期刊：

CIRCULATION RESEARCH ISSN：0009-7330 2015 年 116 卷 1 期 (35 - U98) ; JAN 2
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关键词：

AAV Akt heart failure Hippo PI3 kinase Pik3cb regeneration Yap
摘要：

Rationale: Yes-associated protein (YAP), the nuclear effector of Hippo signaling, regulates cellular growth and survival in multiple organs, including the heart, by interacting with TEA (transcriptional enhancer activator)domain sequence-specific DNA-binding proteins. Recent studies showed that YAP stimulates cardiomyocyte proliferation and survival. However, the direct transcriptional targets through which YAP exerts its effects are poorly defined.
Objective: To identify direct YAP targets that mediate its mitogenic and antiapoptotic effects in the heart.
Methods and Results: We identified direct YAP targets by combining differential gene expression analysis in YAP gain-and loss-of-function with genome-wide identification of YAP-bound loci using chromatin immunoprecipitation and high throughput sequencing. This screen identified Pik3cb, encoding p110 beta, a catalytic subunit of phosphoinositol-3-kinase, as a candidate YAP effector that promotes cardiomyocyte proliferation and survival. YAP and TEA-domain occupied a conserved enhancer within the first intron of Pik3cb, and this enhancer drove YAP-dependent reporter gene expression. Yap gain-and loss-of-function studies indicated that YAP is necessary and sufficient to activate the phosphoinositol-3-kinase-Akt pathway. Like Yap, Pik3cb gain-of-function stimulated cardiomyocyte proliferation, and Pik3cb knockdown dampened YAP mitogenic activity. Reciprocally, impaired heart function in Yap loss-of-function was significantly rescued by adeno-associated virus-mediated Pik3cb expression.
Conclusions: Pik3cb is a crucial direct target of YAP, through which the YAP activates phosphoinositol-3-kinase-AKT pathway and regulates cardiomyocyte proliferation and survival.
推荐引用方式
GB/T 7714：

Lin Zhiqiang,Zhou Pingzhu,von Gise Alexander, et al. Pi3kcb Links Hippo-YAP and PI3K-AKT Signaling Pathways to Promote Cardiomyocyte Proliferation and Survival [J].CIRCULATION RESEARCH,2015,116(1):35-U98.
APA：

Lin Zhiqiang,Zhou Pingzhu,von Gise Alexander,Gu Fei,&Pu William T..(2015).Pi3kcb Links Hippo-YAP and PI3K-AKT Signaling Pathways to Promote Cardiomyocyte Proliferation and Survival .CIRCULATION RESEARCH,116(1):35-U98.
MLA：

Lin Zhiqiang, et al. "Pi3kcb Links Hippo-YAP and PI3K-AKT Signaling Pathways to Promote Cardiomyocyte Proliferation and Survival" .CIRCULATION RESEARCH 116,1(2015):35-U98.
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