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学科主题基础医学
Dok-5 is involved in cardiomyocyte differentiation through PKB/FOXO3a pathway
Wen, Jianyan1,2,3; Xia, Qing4; Wang, Cheng5; Liu, Wei1,2; Chen, Yang1,2; Gao, Jing1,2; Gong, Yanhua1,2; Yin, Bin1,2; Ke, Yuannan3; Qiang, Boqin1,2; Yuan, Jiangang1,2; Peng, Xiaozhong1,2
关键词Dok-5 Foxo3a P19cl6 Cardiomyocyte Differentiation
刊名JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
2009-12-01
DOI10.1016/j.yjmcc.2009.09.015
47期:6页:761-769
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Cell Biology
研究领域[WOS]Cardiovascular System & Cardiology ; Cell Biology
关键词[WOS]FOXO TRANSCRIPTION FACTORS ; INSULIN-RECEPTOR ; CARDIAC MYOGENESIS ; P19CL6 CELLS ; KINASE ; MOUSE ; FEEDBACK ; FAMILY ; IDENTIFICATION ; CSX/NKX-2.5
英文摘要

The insulin receptor substrate (IRS) family plays important roles in cellular growth, signaling, and survival in the brain. We identified IRS6/Dok-5, a member of the IRS family, also expressed in heart. Dok-5 expression level significantly increased during cardiomyocyte differentiation of P19CL6 cells. To understand the mechanism of Dok-5 gene expression and regulation during cardiomyocyte differentiation, we first mapped the transcription start site of the mouse Dok-5 gene and characterized its promoter regions. Truncation and mutation analysis of the Dok-5 promoter identified the forkhead binding element responsible for the repression of Dok-5 promoter activation. The co-localization of FOXO3a and Dok-5 in the mouse heart allows FOXO3a to be a transcriptional regulator of Dok-5. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay confirmed that FOXO3a, could bind to the Dok-5 promoter, accompanied by FOXO3a translocation from the nucleus to cytoplasm. FOXO3a overexpression could inhibit Dok-5 promoter activity. Silencing FOXO3a expression by siRNA upregulated the expression of Dok-5 and enhanced cardiomyocyte differentiation. Moreover, Dok-5 siRNA attenuated cardiomyocyte differentiation. Our results provide the first evidence that FOXO3a, the PI3K/PKB downstream substrate, acts as a transcriptional repressor to inhibit the expression of Dok-5. Dok-5 is involved in cardiomyocyte differentiation by a PI3K/PKB/FOXO3a signaling pathway. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved.

语种英语
WOS记录号WOS:000271984500003
项目编号30600166 ; 30700323 ; 30421003 ; 30430200 ; 2004CB518604 ; 2006CB504100 ; 2006AA02Z137
资助机构National Sciences Foundation of China ; National Program for the Key Basic Research Project ; Hi-Tech Research and Development Program of China
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52847
专题北京大学基础医学院_心血管所
北京大学基础医学院
作者单位1.Chinese Acad Med Sci, Inst Basic Med Sci, Natl Key Lab Med Mol Biol, Beijing 100005, Peoples R China
2.Peking Union Med Coll, Beijing 100005, Peoples R China
3.China Japan Friendship Hosp, Natl Integrat Med Ctr Cardiovasc Dis, Beijing 100029, Peoples R China
4.Beijing Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
5.Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Dept Physiol & Pathophysiol,Minist Educ, Beijing 100191, Peoples R China
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GB/T 7714
Wen, Jianyan,Xia, Qing,Wang, Cheng,et al. Dok-5 is involved in cardiomyocyte differentiation through PKB/FOXO3a pathway[J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,2009,47(6):761-769.
APA Wen, Jianyan.,Xia, Qing.,Wang, Cheng.,Liu, Wei.,Chen, Yang.,...&Peng, Xiaozhong.(2009).Dok-5 is involved in cardiomyocyte differentiation through PKB/FOXO3a pathway.JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,47(6),761-769.
MLA Wen, Jianyan,et al."Dok-5 is involved in cardiomyocyte differentiation through PKB/FOXO3a pathway".JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 47.6(2009):761-769.
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