beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2

	beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2
	Wang, P; Gao, H; Ni, YX; Wang, BB; Wu, YL; Ji, LL; Qin, LH; Ma, L; Pei, G
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2003
卷号	278 期号:8 页码:6363-6370
通讯作者	Pei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,
英文摘要	Oncoprotein Mdm2 is a master negative regulator of the tumor suppressor p53 and has been recently shown to regulate the ubiquitination of beta-arrestin 2, an important adapter and scaffold in signaling of G-protein-coupled receptors (GPCRs). However, whether beta-arrestin 2 has any effect on the function of Mdm2 is still unclear. Our current results demonstrated that the binding of Mdm2 to beta-arrestin 2 was significantly enhanced by stimulation of GPCRs. Activation of GPCRs led to formation of a ternary complex of Mdm2, beta-arrestin 2, and GPCRs and thus recruited Mdm2 to GPCRs at plasma membrane. Moreover, the binding of beta-arrestin 2 to Mdm2 suppressed the self-ubiquitination of Mdm2 and consequently reduced the Mdm2-mediated p53 degradation and ubiquitination. Further experiments revealed that overexpression of beta-arrestin 2 enhanced the p53-mediated apoptosis while suppression of endogenous beta-arrestin 2 expression by RNA interference technology considerably attenuated the p53-mediated apoptosis. Our study thus suggests that beta-arrestin 2 may serve as a cross-talk linker between GPCR and p53 signaling pathways.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	TUMOR-SUPPRESSOR P53 ; INTRACELLULAR DOMAINS ; INDUCED APOPTOSIS ; NUCLEAR EXPORT ; PATHWAY ; STABILITY ; INTERNALIZATION ; COMPLEXES ; KINASE ; MAPK
收录类别	SCI
语种	英语
WOS记录号	WOS:000181129400110
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2340]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Wang, P,Gao, H,Ni, YX,et al. beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2003,278(8):6363-6370.
APA	Wang, P.,Gao, H.,Ni, YX.,Wang, BB.,Wu, YL.,...&Pei, G.(2003).beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2.JOURNAL OF BIOLOGICAL CHEMISTRY,278(8),6363-6370.
MLA	Wang, P,et al."beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2".JOURNAL OF BIOLOGICAL CHEMISTRY 278.8(2003):6363-6370.