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	Human cytomegalovirus ie1 downregulates hes1 in neural progenitor cells as a potential e3 ubiquitin ligase
	Liu, Xi-Juan1,2; Yang, Bo1; Huang, Sheng-Nan1; Wu, Cong-Cong1; Li, Xiao-Jun1; Cheng, Shuang1; Jiang, Xuan1,3; Hu, Fei4; Ming, Ying-Zi5; Nevels, Michael6
刊名	Plos pathogens
	2017-07-01
卷号	13期号:7页码:28
ISSN号	1553-7366
DOI	10.1371/journal.ppat.1006542
通讯作者	Zeng, wen-bo(zengwb@wh.iov.cn) ; Zhao, fei(zhaofei@wh.iov.cn) ; Luo, min-hua(luomh@wh.iov.cn)
英文摘要	Congenital human cytomegalovirus (hcmv) infection is the leading cause of neurological disabilities in children worldwide, but the mechanisms underlying these disorders are far from well-defined. hcmv infection has been shown to dysregulate the notch signaling pathway in human neural progenitor cells (npcs). as an important downstream effector of notch signaling, the transcriptional regulator hairy and enhancer of split 1 (hes1) is essential for governing npc fate and fetal brain development. in the present study, we report that hcmv infection downregulates hes1 protein levels in infected npcs. the hcmv 72-kda immediate-early 1 protein (ie1) is involved in hes1 degradation by assembling a ubiquitination complex and promoting hes1 ubiquitination as a potential e3 ubiquitin ligase, followed by proteasomal degradation of hes1. sp100a, an important component of pml nuclear bodies, is identified to be another target of ie1-mediated ubiquitination. a c-terminal acidic region in ie1, spanning amino acids 451 to 475, is required for ie1/hes1 physical interaction and ie1-mediated hes1 ubiquitination, but is dispensable for ie1/sp100a interaction and ubiquitination. our study suggests a novel mechanism linking downregulation of hes1 protein to neurodevelopmental disorders caused by hcmv infection. our findings also complement the current knowledge of herpesviruses by identifying ie1 as the first potential hcmv-encoded e3 ubiquitin ligase.
WOS关键词	LOW-MULTIPLICITY INFECTION ; RING FINGER DOMAIN ; GENE-EXPRESSION ; NEURONAL DIFFERENTIATION ; MEDIATED DEGRADATION ; PROTEASOME ACTIVITY ; LYTIC REPLICATION ; VIRAL REPLICATION ; PRECURSOR CELLS ; SP100 PROTEINS
WOS研究方向	Microbiology ; Parasitology ; Virology
WOS类目	Microbiology ; Parasitology ; Virology
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000406623700060
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2373367
专题	武汉病毒研究所
通讯作者	Zeng, Wen-Bo; Zhao, Fei; Luo, Min-Hua
作者单位	1.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, CAS Ctr Excellence Brain Sci & Intelligence Techn, Wuhan, Hubei, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Guangzhou Women & Children Med Ctr, Guangzhou Inst Pediat, Guangzhou, Guangdong, Peoples R China 4.Minist Transportat, Wuhan Brain Hosp, Wuhan, Hubei, Peoples R China 5.South Cent Univ, Xiangya Hosp 3, Changsha, Hunan, Peoples R China 6.Univ St Andrews, Sch Biol, Biomed Sci Res Complex, St Andrews, Fife, Scotland 7.Univ Alabama Birmingham, Sch Med, Dept Pediat, Birmingham, AL USA 8.Oslo Univ Hosp, Dept Med Genet, Oslo, Norway 9.Univ Oslo, Oslo, Norway 10.Howard Univ, Coll Med, Dept Microbiol, Washington, DC USA
推荐引用方式 GB/T 7714	Liu, Xi-Juan,Yang, Bo,Huang, Sheng-Nan,et al. Human cytomegalovirus ie1 downregulates hes1 in neural progenitor cells as a potential e3 ubiquitin ligase[J]. Plos pathogens,2017,13(7):28.
APA	Liu, Xi-Juan.,Yang, Bo.,Huang, Sheng-Nan.,Wu, Cong-Cong.,Li, Xiao-Jun.,...&Luo, Min-Hua.(2017).Human cytomegalovirus ie1 downregulates hes1 in neural progenitor cells as a potential e3 ubiquitin ligase.Plos pathogens,13(7),28.
MLA	Liu, Xi-Juan,et al."Human cytomegalovirus ie1 downregulates hes1 in neural progenitor cells as a potential e3 ubiquitin ligase".Plos pathogens 13.7(2017):28.

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