Opposing Roles for ATF2 and c-Fos in c-Jun-Mediated Neuronal Apoptosis

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	Opposing Roles for ATF2 and c-Fos in c-Jun-Mediated Neuronal Apoptosis
	Wang, Yizheng
刊名	MOLECULAR AND CELLULAR BIOLOGY
	2009
卷号	29 期号:9 页码:2431-2442
关键词	CEREBELLAR GRANULE NEURONS N-TERMINAL KINASE ACTIVATED PROTEIN-KINASES PROGRAMMED CELL-DEATH GENE-EXPRESSION TRANSCRIPTION FACTOR POTASSIUM DEPRIVATION FAS LIGAND SYMPATHETIC NEURONS RESPONSE ELEMENT
ISSN号	0270-7306
通讯作者	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
英文摘要	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.
学科主题	Biochemistry & Molecular Biology ; Cell Biology
收录类别	SCI
资助信息	National Natural Science Foundation of China[U0632006, 30870786, 30629002, 30831160511]
语种	英语
公开日期	2012-07-13
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1662]
专题	上海神经科学研究所_神经所(总) 上海神经科学研究所_神经信号转导研究组
推荐引用方式 GB/T 7714	Wang, Yizheng. Opposing Roles for ATF2 and c-Fos in c-Jun-Mediated Neuronal Apoptosis[J]. MOLECULAR AND CELLULAR BIOLOGY,2009,29(9):2431-2442.
APA	Wang, Yizheng.(2009).Opposing Roles for ATF2 and c-Fos in c-Jun-Mediated Neuronal Apoptosis.MOLECULAR AND CELLULAR BIOLOGY,29(9),2431-2442.
MLA	Wang, Yizheng."Opposing Roles for ATF2 and c-Fos in c-Jun-Mediated Neuronal Apoptosis".MOLECULAR AND CELLULAR BIOLOGY 29.9(2009):2431-2442.