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	Identification of an adaptor protein that facilitates nrf2-keap1 complex formation and modulates antioxidant response
	Zhang, Yuxue1; Hou, Yongfan1; Liu, Chunchun1; Li, Yinlong2; Guo, Weiwei1; Wu, Jiu-Lin3; Xu, Daqian1; You, Xue1,4; Pan, Yi1; Chen, Yan1
刊名	Free radical biology and medicine
	2016-08-01
卷号	97页码:38-49
关键词	Nrf2 Keap1 Antioxidant Ubiquitination Paqr3 Golgi apparatus
ISSN号	0891-5849
DOI	10.1016/j.freeradbiomed.2016.05.017
通讯作者	Chen, yan(ychen3@sibs.ac.cn)
英文摘要	Nrf2 plays a key role in the protection of the body against environmental stress via inducible expression of detoxification and antioxidant enzymes. keapl functions as a sensor for oxidative and electrophilic stresses and promotes nrf2 degradation via its e3 ligase activity. modulation of the nrf2-keap1 pathway has been extensively explored as a strategy to combat against drug toxicity and stress-induced diseases. here we report a new player that modulates the nrf2-keap1 pathway. paqr3, a membrane protein specifically localized in the golgi apparatus, negatively regulates the expression of an array of nrf2 target genes and alters cellular level of reactive oxygen species. paqr3 tethers nrf2 and keapl, but not small maf proteins to the golgi apparatus. paqr3 interacts with both nrf2 and keapl and facilitates the interaction of nrf2 with keapl. paqr3 promotes ubiquitination and degradation of nrf2. disruption of paqr3 interaction with nrf2 and keapl by a synthetic peptide reduces nrf2 ubiquitination and elevates expression of nrf2 target genes. at the animal level, deletion of paqr3 increases nrf2 protein level and the expression of nrf2 target genes. in conclusion, our study pinpoints that paqr3 functions as an adaptor protein to promote nrf2-keap1 complex formation, thereby modulating the nrf2-keap2 pathway and playing an important role in controlling antioxidant response of the cell. (c) 2016 elsevier inc. all rights reserved.
WOS关键词	PLACEBO-CONTROLLED PHASE-3 ; OXIDATIVE STRESS ; HEPATOCELLULAR-CARCINOMA ; TRANSCRIPTION FACTOR ; MULTIPLE-SCLEROSIS ; BARDOXOLONE METHYL ; TUMOR-SUPPRESSOR ; GOLGI-APPARATUS ; ORAL BG-12 ; NRF2
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS类目	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000381924100004
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2376342
专题	中国科学院大学
通讯作者	Chen, Yan
作者单位	1.Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Chinese Acad Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai 200031, Peoples R China 2.Chinese Ctr Dis Control & Prevent, Natl Inst Parasit Dis, Shanghai 200336, Peoples R China 3.Fuzhou Univ, Inst Biomed & Pharmaceut Technol, Fuzhou 350002, Peoples R China 4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Yuxue,Hou, Yongfan,Liu, Chunchun,et al. Identification of an adaptor protein that facilitates nrf2-keap1 complex formation and modulates antioxidant response[J]. Free radical biology and medicine,2016,97:38-49.
APA	Zhang, Yuxue.,Hou, Yongfan.,Liu, Chunchun.,Li, Yinlong.,Guo, Weiwei.,...&Chen, Yan.(2016).Identification of an adaptor protein that facilitates nrf2-keap1 complex formation and modulates antioxidant response.Free radical biology and medicine,97,38-49.
MLA	Zhang, Yuxue,et al."Identification of an adaptor protein that facilitates nrf2-keap1 complex formation and modulates antioxidant response".Free radical biology and medicine 97(2016):38-49.

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