c-Jun Protects Hypoxia-Inducible Factor-1 alpha from Degradation via Its Oxygen-Dependent Degradation Domain in a Nontranscriptional Manner

doi:10.1158/0008-5472.CAN-09-0808

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	c-Jun Protects Hypoxia-Inducible Factor-1 alpha from Degradation via Its Oxygen-Dependent Degradation Domain in a Nontranscriptional Manner
	Yu, Bing; Miao, Ze-Hong; Jiang, Yi; Li, Mei-Hong; Yang, Na; Li, Ting; Ding, Jian
刊名	CANCER RESEARCH
	2009-10-01
卷号	69 期号:19 页码:7704-7712
ISSN号	0008-5472
DOI	10.1158/0008-5472.CAN-09-0808
文献子类	Article
英文摘要	Although hypoxia-inducible factor-1 alpha (HIF-1 alpha) has long been intensively investigated as a drug target by interfering with its expression or transcriptional function, the regulatory mechanisms of HIF-1 alpha remain to be further clarified. We report here that c-Jun associates with HIF-1 alpha via its oxygen-dependent degradation domain, masks the sites for ubiquitination, and thus protects HIF-1 alpha from proteasome-executing degradation. All of these together resulted in the stabilization and accumulation of HIF-1 alpha, consequently promoting the transcription of its target gene and driving angiogenesis-related events. The stabilization of HIF-1 alpha was dependent on the domains of c-Jun for DNA binding and heterodimerization but independent. of the Ser(63/73) phosphorylation that is critical for transcriptional function. These findings highlight a previously unrecognized nontranscriptional function of c-Jun on the one hand and a distinct regulatory mechanism of HIF-1 alpha activity on the other, consequently offering profound mechanistic insights into multiple events simultaneously involving both c-Jun and HIF-1 alpha in tumor progression. [Cancer Res 2009;69(19):7704-12]
资助项目	National Natural Sciences Foundation of China[30730103] ; National Natural Sciences Foundation of China[30721005] ; Science and Technology Commission of Shanghai Municipality[08DZ1980200]
WOS关键词	ENDOTHELIAL GROWTH-FACTOR ; HIPPEL-LINDAU PROTEIN ; TUMOR-SUPPRESSOR PROTEIN ; FACTOR 1-ALPHA ; TRANSCRIPTIONAL ACTIVITY ; PROLYL HYDROXYLATION ; GENE-TRANSCRIPTION ; SIGNALING PATHWAY ; HIF-ALPHA ; ANGIOGENESIS
WOS研究方向	Oncology
语种	英语
出版者	AMER ASSOC CANCER RESEARCH
WOS记录号	WOS:000270487600029
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279107]
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	Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Yu, Bing,Miao, Ze-Hong,Jiang, Yi,et al. c-Jun Protects Hypoxia-Inducible Factor-1 alpha from Degradation via Its Oxygen-Dependent Degradation Domain in a Nontranscriptional Manner[J]. CANCER RESEARCH,2009,69(19):7704-7712.
APA	Yu, Bing.,Miao, Ze-Hong.,Jiang, Yi.,Li, Mei-Hong.,Yang, Na.,...&Ding, Jian.(2009).c-Jun Protects Hypoxia-Inducible Factor-1 alpha from Degradation via Its Oxygen-Dependent Degradation Domain in a Nontranscriptional Manner.CANCER RESEARCH,69(19),7704-7712.
MLA	Yu, Bing,et al."c-Jun Protects Hypoxia-Inducible Factor-1 alpha from Degradation via Its Oxygen-Dependent Degradation Domain in a Nontranscriptional Manner".CANCER RESEARCH 69.19(2009):7704-7712.