An NADPH sensor protein (HSCARG) down-regulates nitric oxide synthesis   by association with argininosuccinate synthetase and is essential for   epithelial cell viability

doi:10.1074/jbc.M708697200

CORC > 北京大学 > 生命科学学院

	An NADPH sensor protein (HSCARG) down-regulates nitric oxide synthesis by association with argininosuccinate synthetase and is essential for epithelial cell viability
	Zhao, Yanmei ; Zhang, Jinfang ; Li, Huiying ; Li, Yiyu ; Ren, Jie ; Luo, Ming ; Zheng, Xiaofeng
刊名	journal of biological chemistry
	2008
关键词	VASCULAR SMOOTH-MUSCLE ENDOTHELIAL-CELLS CANCER BIOLOGY NO PRODUCTION L-ARGININE APOPTOSIS DISEASE EXPRESSION SYNTHASE BINDING
DOI	10.1074/jbc.M708697200
英文摘要	NADPH is an important cofactor in many biosynthesis pathways that control fundamental cellular processes. We recently determined the crystal structure of HSCARG, with functions previously unknown, and demonstrated it is an NADPH sensor, which undergoes restructuring and redistribution in response to changes of intracellular NADPH/NADP levels. In this study, we identified argininosuccinate synthetase (AS), a rate-limiting enzyme in nitric oxide synthesis, as capable of associating with HSCARG and demonstrated further that HSCARG decreased nitric oxide synthesis by down-regulating AS activity, whereas AS overexpression up-regulated hscarg mRNA transcription, suggesting a negative feedback mechanism. A decrease in the NADPH/NADP(+) ratio, induced by dehydroepiandrosterone treatment, enhanced the interaction between HSCARG and AS, which resulted in stronger inhibition of AS activity and nitric oxide production. The dimerization region of HSCARG, amino acids 153-189, was identified to undergo critical interactions with AS. Furthermore, the viability of HSCARG RNA interference-treated epithelial cells decreased significantly, accompanied by an increase of the activity of caspase-3, which suggested that the loss of viability was because of apoptosis. These results indicate that HSCARG regulation of AS activity is crucial for maintaining the intracellular balance between redox state and nitric oxide levels.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000254894700081&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Biochemistry & Molecular Biology; SCI(E); EI; PubMed; 27; ARTICLE; 16; 11004-11013; 283
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/320027]
专题	生命科学学院
推荐引用方式 GB/T 7714	Zhao, Yanmei,Zhang, Jinfang,Li, Huiying,et al. An NADPH sensor protein (HSCARG) down-regulates nitric oxide synthesis by association with argininosuccinate synthetase and is essential for epithelial cell viability[J]. journal of biological chemistry,2008.
APA	Zhao, Yanmei.,Zhang, Jinfang.,Li, Huiying.,Li, Yiyu.,Ren, Jie.,...&Zheng, Xiaofeng.(2008).An NADPH sensor protein (HSCARG) down-regulates nitric oxide synthesis by association with argininosuccinate synthetase and is essential for epithelial cell viability.journal of biological chemistry.
MLA	Zhao, Yanmei,et al."An NADPH sensor protein (HSCARG) down-regulates nitric oxide synthesis by association with argininosuccinate synthetase and is essential for epithelial cell viability".journal of biological chemistry (2008).