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学科主题: 临床医学
题名:
Neurodegeneration-associated TDP-43 Interacts with Fragile X Mental Retardation Protein (FMRP)/Staufen (STAU1) and Regulates SIRT1 Expression in Neuronal Cells
作者: Yu, Zhipeng1; Fan, Dongsheng1; Gui, Bin1; Shi, Lei2; Xuan, Chenghao2; Shan, Lin2; Wang, Qian2; Shang, Yongfeng2; Wang, Yan2
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2012-06-29
DOI: 10.1074/jbc.M112.357582
卷: 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
所属项目编号: 90919053 ; 31171240 ; 81030019
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000306495000013
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55320
Appears in Collections:北京大学第三临床医学院_期刊论文

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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

Recommended Citation:
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.
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