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The LIM-Homeodomain Protein ISL1 Activates Insulin Gene Promoter Directly through Synergy with BETA2
Zhang, Hui1; Wang, Wei-Ping1; Guo, Ting1; Yang, Ji-Chun2; Chen, Ping1; Ma, Kang-Tao1; Guan, You-Fei2; Zhou, Chun-Yan1
关键词ISL1 BETA2 insulin gene expression protein interactions transcriptional factors
刊名JOURNAL OF MOLECULAR BIOLOGY
2009-09-25
DOI10.1016/j.jmb.2009.07.036
392期:3页:566-577
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]LOOP-HELIX PROTEIN ; TRANSCRIPTIONAL SYNERGY ; ENDOCRINE-CELLS ; BINDING-PROTEIN ; FACTOR-I ; EXPRESSION ; DOMAIN ; PDX-1 ; RAT ; DIFFERENTIATION
英文摘要

The LIM-homeodomain transcription factor ISM (islet factor 1) is essential for pancreatic islet cell and dorsal mesenchyme development. Mutations in ISL1 are associated with maturity-onset diabetes of the young and type 2 diabetes. Whether ISL1 plays a role in the insulin gene expression has not been fully elucidated. In the present study, we show that ISL1 can synergistically activate insulin gene transcription with BETA2 in pancreatic P cells. The protein-protein interactions of ISL1 and BETA2 are directly mediated by the LIM domains of ISL1 and the basic helix-loop-helix domain of BETA2. Deletion of the two LIM domains of ISM enhances the transcriptional activation of the insulin gene, indicating a key role for the homeodomain in activating the insulin promoter. Furthermore, ISL1 can bind with the A3/4 box in the rat insulin gene I promoter through its homeodomain. ISL1 expression is up-regulated at the mRNA level in type 2 diabetes (db/db mouse model) but down-regulated by dexamethasone in rat insulinoma cells. These results suggest that ISL1 is a transcriptional activator for insulin gene expression, and the interactions of ISM with BETA2 are required for the transcriptional activity of the insulin gene. Reduction in Isl1 gene expression appears to be involved in the impairment of insulin expression mediated by dexamethasone. (C) 2009 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000270317700002
项目编号30470402 ; 1307001 ; 20060001107 ; PUDC2007-5
资助机构National Natural Science Foundation of China ; The 111 Project of China ; Specialized Research Fund for the Doctoral Program of Higher Education ; Project Foundation of Diabetes Center of Peking University
引用统计
被引频次:24[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/400002259/62529
专题北京大学基础医学院
北京大学药学院_药学院
北京大学临床肿瘤学院_603课题组
作者单位1.Peking Univ, Dept Biochem & Mol Biol, Sch Basic Med Sci, Beijing 100191, Peoples R China
2.Peking Univ, Dept Physiol, Sch Basic Med Sci, Ctr Diabet, Beijing 100191, Peoples R China
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GB/T 7714
Zhang, Hui,Wang, Wei-Ping,Guo, Ting,et al. The LIM-Homeodomain Protein ISL1 Activates Insulin Gene Promoter Directly through Synergy with BETA2[J]. JOURNAL OF MOLECULAR BIOLOGY,2009,392(3):566-577.
APA Zhang, Hui.,Wang, Wei-Ping.,Guo, Ting.,Yang, Ji-Chun.,Chen, Ping.,...&Zhou, Chun-Yan.(2009).The LIM-Homeodomain Protein ISL1 Activates Insulin Gene Promoter Directly through Synergy with BETA2.JOURNAL OF MOLECULAR BIOLOGY,392(3),566-577.
MLA Zhang, Hui,et al."The LIM-Homeodomain Protein ISL1 Activates Insulin Gene Promoter Directly through Synergy with BETA2".JOURNAL OF MOLECULAR BIOLOGY 392.3(2009):566-577.
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