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Quantitative integration of epigenomic variation and transcription factor binding using MAmotif toolkit identifies an important role of IRF2 as transcription activator at gene promoters

文献类型：期刊论文

作者Sun, Hongduo2,3; Gong, Zhaohui2; Yao, Jiaying2,3; Wang, Yuangao2; Shao, Zhen2; Wang, Jiawei4; Zhang, Yijing4; Xu, Jian5; Yuan, Guo-cheng1,6,7; ,
刊名CELL DISCOVERY
出版日期2018
卷号4期号:-页码:38
关键词Circadian rhythm Rhythmically expressed gene Rhythmic gene function Energy cost
ISSN号2056-5968
DOI10.1038/s41421-018-0045-y
文献子类Letter
英文摘要Targeting apoptosis of vascular smooth muscle cells (VSMCs) represents an attractive approach to diminish the occurrence of restenosis. Neddylation is a highly conserved post-translational modification process and inhibition of neddylation has been shown to regulate apoptosis of other cells. However, the impacts of neddylation inhibition on VSMCs and neointimal hyperplasia have not been studied. In our present study, we have shown that MLN4924, a selective inhibitor of NEDD8-activating enzyme (NAE), markedly inhibited neointimal hyperplasia and accumulation of VSMCs, whereas increased apoptosis in the vascular wall. In vitro studies revealed that MLN4924 induced G2/M arrest and apoptosis of human VSMCs. Knockdown of NAE1 had similar effects. MLN4924 upregulated p53 and p62 in human VSMCs. Knockdown of either p53 or p62 mitigated the impacts of MLN4924 on G2/M arrest and apoptosis. Moreover, p53 knockdown abolished MLN4924-induced upregulation of p62. Finally, smooth muscle p53 knockout mice were generated and subjected to femoral artery injury and MLN4924 treatment. Deficiency of p53 in smooth muscle blocked the effects of MLN4924 on neointimal hyperplasia and apoptosis. Together, our results revealed that neddylation inhibition induces apoptosis through p53 and p62 in VSMCs and improves neointimal hyperplasia mainly by promoting apoptosis through smooth muscle p53 in mice. These pre-clinical data provide strong translational implications for targeting restenosis by perturbation of neddylation using MLN4924.
学科主题Cell Biology
WOS关键词EXPRESSION ; ENHANCERS
语种英语
CSCD记录号CSCD:31747875
WOS记录号WOS:000437846600001
出版者NATURE PUBLISHING GROUP
版本出版稿
源URL[http://202.127.25.144/handle/331004/825]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Harvard Stem Cell Inst, Cambridge, MA 02138 USA,
2.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China;
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China;
4.Chinese Acad Sci, Shanghai Inst Plant Physiol & Ecol, Shanghai Inst Biol Sci, Natl Key Lab Plant Mol Genet,CAS Ctr Excellence M, Shanghai 200032, Peoples R China;
5.Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Res Inst, Childrens Med Ctr, Dallas, TX 75390 USA;
6.Harvard TH Chan Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA;
7.Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA;
推荐引用方式
GB/T 7714		 Sun, Hongduo,Gong, Zhaohui,Yao, Jiaying,et al. Quantitative integration of epigenomic variation and transcription factor binding using MAmotif toolkit identifies an important role of IRF2 as transcription activator at gene promoters[J]. CELL DISCOVERY,2018,4(-):38.
APA Sun, Hongduo.,Gong, Zhaohui.,Yao, Jiaying.,Wang, Yuangao.,Shao, Zhen.,...&,.(2018).Quantitative integration of epigenomic variation and transcription factor binding using MAmotif toolkit identifies an important role of IRF2 as transcription activator at gene promoters.CELL DISCOVERY,4(-),38.
MLA Sun, Hongduo,et al."Quantitative integration of epigenomic variation and transcription factor binding using MAmotif toolkit identifies an important role of IRF2 as transcription activator at gene promoters".CELL DISCOVERY 4.-(2018):38.

入库方式： OAI收割

来源：上海营养与健康研究所

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