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Neurodegeneration-associated TDP-43 Interacts with Fragile X Mental Retardation Protein (FMRP)/Staufen (STAU1) and Regulates SIRT1 Expression in Neuronal Cells
Yu, Zhipeng1; Fan, Dongsheng1; Gui, Bin1; Shi, Lei2; Xuan, Chenghao2; Shan, Lin2; Wang, Qian2; Shang, Yongfeng2; Wang, Yan2
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
2012-06-29
DOI10.1074/jbc.M112.357582
287期:27页:22560-22572
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]AMYOTROPHIC-LATERAL-SCLEROSIS ; NUCLEAR FACTOR TDP-43 ; DNA-BINDING PROTEIN ; FRONTOTEMPORAL LOBAR DEGENERATION ; MESSENGER-RNA TRANSPORT ; FUNCTIONAL IMPLICATIONS ; TRANSCRIPTION FACTORS ; HIPPOCAMPAL-NEURONS ; ALZHEIMERS-DISEASE ; TARDBP MUTATIONS
英文摘要

Despite the identification of the 43 kDa transactive response DNA- binding protein (TDP-43) as a major pathological signatory protein in a wide range of neurodegenerative diseases, the mechanistic role of TDP-43 in neurodegenerative disorders is still poorly understood. Here, we report that TDP-43 is physically associated with fragile X mental retardation protein (FMRP) and Staufen (STAU1) to form a functional complex. Differential microarray analysis revealed that the expression of a collection of functionally important genes including Sirtuin (SIRT1) is regulated by this complex. RNA-immunoprecipitation (RIP) and RNA pull-down assays demonstrated that TDP43/FMRP/STAU1 specifically binds to the 3′-UTR of SIRT1 mRNA, and that knockdown the expression of any one of these three proteins resulted in the reduction of SIRT1 mRNA and protein. SIRT1 is implicated in double-stranded DNA break repair and is required for cell survival. Indeed, depletion of TDP-43/FMRP/STAU1 sensitizes cells to apoptosis and DNA damages. Collectively, our results revealed a molecular mechanism for the cellular function of TDP-43 and might shed new light on the understanding of the mechanistic role of TDP-43 in neurodegenerative diseases.

语种英语
WOS记录号WOS:000306495000013
项目编号90919053 ; 31171240 ; 81030019
资助机构National Natural Science Foundation of China
引用统计
被引频次:22[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/400002259/55320
专题北京大学第三临床医学院
北京大学第三临床医学院_神经内科
作者单位1.Peking Univ, Hosp 3, Beijing 100191, Peoples R China
2.Tianjin Med Univ, Dept Biochem & Mol Biol, Tianjin Key Lab Med Epigenet, Tianjin 300070, Peoples R China
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GB/T 7714
Yu, Zhipeng,Fan, Dongsheng,Gui, Bin,et al. Neurodegeneration-associated TDP-43 Interacts with Fragile X Mental Retardation Protein (FMRP)/Staufen (STAU1) and Regulates SIRT1 Expression in Neuronal Cells[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(27):22560-22572.
APA Yu, Zhipeng.,Fan, Dongsheng.,Gui, Bin.,Shi, Lei.,Xuan, Chenghao.,...&Wang, Yan.(2012).Neurodegeneration-associated TDP-43 Interacts with Fragile X Mental Retardation Protein (FMRP)/Staufen (STAU1) and Regulates SIRT1 Expression in Neuronal Cells.JOURNAL OF BIOLOGICAL CHEMISTRY,287(27),22560-22572.
MLA Yu, Zhipeng,et al."Neurodegeneration-associated TDP-43 Interacts with Fragile X Mental Retardation Protein (FMRP)/Staufen (STAU1) and Regulates SIRT1 Expression in Neuronal Cells".JOURNAL OF BIOLOGICAL CHEMISTRY 287.27(2012):22560-22572.
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