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Title: Opposing Roles for ATF2 and c-Fos in c-Jun-Mediated Neuronal Apoptosis
Author: Yuan, Zhongmin ; Gong, Shoufang ; Luo, Jingyan ; Zheng, Zhihao ; Song, Bin ; Ma, Shanshan ; Guo, Jiaoli ; Hu, Ce ; Thiel, Gerald ; Vinson, Charles ; Hu, Chang-Deng ; null(王以政) ; Li, Mingtao
Source: MOLECULAR AND CELLULAR BIOLOGY
Issued Date: 2009
Volume: 29, Issue:9, Pages:2431-2442
Keyword: CEREBELLAR GRANULE NEURONS ; N-TERMINAL KINASE ; ACTIVATED PROTEIN-KINASES ; PROGRAMMED CELL-DEATH ; GENE-EXPRESSION ; TRANSCRIPTION FACTOR ; POTASSIUM DEPRIVATION ; FAS LIGAND ; SYMPATHETIC NEURONS ; RESPONSE ELEMENT
Subject: Biochemistry & Molecular Biology ; Cell Biology
Corresponding Author: Li, MT (reprint author), Sun Yat Sen Univ, Zhongshan Sch Med, Dept Pharmacol, 74 Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China,limt@mail.sysu.edu.cn
English Abstract: The activator protein 1 (AP-1) transcription factor c-Jun is crucial for neuronal apoptosis. However, c-Jun dimerization partners and the regulation of these proteins in neuronal apoptosis remain unknown. Here we report that c-Jun-mediated neuronal apoptosis requires the concomitant activation of activating transcription factor-2 (ATF2) and downregulation of c-Fos. Furthermore, we have observed that c-Jun predominantly heterodimerizes with ATF2 and that the c-Jun/ATF2 complex promotes apoptosis by triggering ATF activity. Inhibition of c-Jun/ATF2 heterodimerization using dominant negative mutants, small hairpin RNAs, or decoy oligonucleotides was able to rescue neurons from apoptosis, whereas constitutively active ATF2 and c-Jun mutants were found to synergistically stimulate apoptosis. Bimolecular fluorescence complementation analysis confirmed that, in living neurons, c-Fos downregulation facilitates c-Jun/ATF2 heterodimerization. A chromatin immunoprecipitation assay also revealed that c-Fos expression prevents the binding of c-Jun/ATF2 heterodimers to conserved ATF sites. Moreover, the presence of c-Fos is able to suppress the expression of c-Jun/ATF2-mediated target genes and, therefore, apoptosis. Taken together, our findings provide evidence that potassium deprivation-induced neuronal apoptosis is mediated by concurrent upregulation of c-Jun/ATF2 heterodimerization and downregulation of c-Fos expression. This paradigm demonstrates opposing roles for ATF2 and c-Fos in c-Jun-mediated neuronal apoptosis.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1662
Appears in Collections:神经所(总)_期刊论文
神经信号转导研究组_期刊论文

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Yuan, Zhongmin; Gong, Shoufang; Luo, Jingyan; Zheng, Zhihao; Song, Bin; Ma, Shanshan; Guo, Jiaoli; Hu, Ce; Thiel, Gerald; Vinson, Charles; Hu, Chang-Deng; Wang, Yizheng; Li, Mingtao.Opposing Roles for ATF2 and c-Fos in c-Jun-Mediated Neuronal Apoptosis,MOLECULAR AND CELLULAR BIOLOGY,2009,29(9):2431-2442
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