Pseudolaric acid B-driven phosphorylation of c-Jun impairs its role in stabilizing HIF-1alpha: a novel function-converter model

doi:10.1007/s00109-012-0865-4

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Pseudolaric acid B-driven phosphorylation of c-Jun impairs its role in stabilizing HIF-1alpha: a novel function-converter model
	Yu, Bing 1; Li, Mei-Hong 1; Wang, Wei 1; Wang, Ying-Qing1 ; Jiang, Yi1 ; Yang, Sheng-Ping 2; Yue, Jian-Min2 ; Ding, Jian1 ; Miao, Ze-Hong 1
刊名	JOURNAL OF MOLECULAR MEDICINE-JMM
	2012-08
卷号	90 期号:8 页码:971-981
关键词	c-Jun Hypoxia inducible factor 1 alpha JNK Pseudolaric acid B Ser63/73 phosphorylation
ISSN号	0946-2716
DOI	10.1007/s00109-012-0865-4
文献子类	Article
英文摘要	We have recently discovered that c-Jun executes a non-transcriptional function to stabilize hypoxia inducible factor 1 alpha (HIF-1 alpha) and that pseudolaric acid B (PAB) accelerates HIF-1 alpha degradation and phosphorylates c-Jun at Ser63/73. In this study, PAB was used as a probe to investigate whether and how the Ser63/73 phosphorylation of c-Jun regulates its functions. The PAB-induced reduction of HIF-1 alpha protein was rescued through supplying additional non-phosphorylated c-Jun. However, c-Jun siRNA, which reduced both the PAB-driven phosphorylated c-Jun and the total c-Jun protein, did not prevent the PAB-induced decrease in HIF-1 alpha. HIF-1 alpha was revealed to be co-immunoprecipitated only with the non-phosphorylated c-Jun. PAB increased the phosphorylated c-Jun while reducing the non-phosphorylated c-Jun at Ser63/73, which impaired its function in stabilizing HIF-1 alpha. Consequently, PAB led to the degradation of HIF-1 alpha, thus resulting in the decreased HIF-1 alpha-dependent expression of mdr-1 and VEGF. We accordingly propose a function-converter model of c-Jun: the Ser63/73 phosphorylation serves as a function converter to convert c-Jun from its non-transcriptional function to its transcriptional function.
资助项目	National Natural Science Foundation of China[81025020] ; National Natural Science Foundation of China[30730103] ; National Natural Science Foundation of China[81021062] ; National Basic Research Program of China[2012CB932502] ; National Science & Technology Major Project of China[2012ZX09301-001-002] ; State Key Laboratory of Biotherapy of China[SKLB200902]
WOS关键词	HYPOXIA-INDUCIBLE FACTOR-1-ALPHA ; MULTIDRUG-RESISTANCE PHENOTYPE ; MDR-1 GENE-EXPRESSION ; NH2-TERMINAL KINASE ; CANCER-CELLS ; HIF-1-ALPHA ; TRANSCRIPTION ; ANGIOGENESIS ; ACTIVATION ; APOPTOSIS
WOS研究方向	Genetics & Heredity ; Research & Experimental Medicine
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000306437700011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278005]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ding, Jian
作者单位	1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Dept Phytochem, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Yu, Bing,Li, Mei-Hong,Wang, Wei,et al. Pseudolaric acid B-driven phosphorylation of c-Jun impairs its role in stabilizing HIF-1alpha: a novel function-converter model[J]. JOURNAL OF MOLECULAR MEDICINE-JMM,2012,90(8):971-981.
APA	Yu, Bing.,Li, Mei-Hong.,Wang, Wei.,Wang, Ying-Qing.,Jiang, Yi.,...&Miao, Ze-Hong.(2012).Pseudolaric acid B-driven phosphorylation of c-Jun impairs its role in stabilizing HIF-1alpha: a novel function-converter model.JOURNAL OF MOLECULAR MEDICINE-JMM,90(8),971-981.
MLA	Yu, Bing,et al."Pseudolaric acid B-driven phosphorylation of c-Jun impairs its role in stabilizing HIF-1alpha: a novel function-converter model".JOURNAL OF MOLECULAR MEDICINE-JMM 90.8(2012):971-981.