|High-throughput screening identifies CHMP4A associated with hypoxia-inducible factor 1|
|Shi, Taiping1,2,3; Dong, Yunqiao1,4; Li, Jing1; Gao, Peng1; Fu, Dongxu1; Ma, Dalong1,2,3|
|关键词||Hypoxia Hypoxia-inducible factor-1 alpha CHMP4A Functional genomics High-throughput screening|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, Research & Experimental ; Pharmacology & Pharmacy|
|研究领域[WOS]||Research & Experimental Medicine ; Pharmacology & Pharmacy|
|关键词[WOS]||SMALL-MOLECULE INHIBITORS ; FACTOR-I ; GENE ; PROTEINS ; DATABASE ; HIF-1|
Aims: Tumor hypoxia is a common phenomenon and hypoxia-inducible factor-1 is the transcription factor that is most closely associated with hypoxia. Hypoxia-inducible factor-1 is overexpressed in most solid tumors and plays a vital role in hypoxic acclimatization, energy metabolism, tumor angiogenesis, tumor invasion, and drug tolerance in cancer cells. We aimed to identify novel human genes associated with the stability and transcriptional activity of hypoxia-inducible factor-1.
Main methods: A cell-based dual luciferase reporter system based on a hypoxia responsive element luciferase reporter gene was constructed to screen 409 novel human genes cloned in our lab. Western blot analysis was used to examine the changes in the expression level of hypoxia-inducible factor-1 alpha, and RT-PCR analysis was used to detect the transcription level of adenylate kinase 3.
Key findings: Our results demonstrated that chromatin-modifying protein 4A could significantly up-regulate the hypoxia responsive element luciferase activity under both normoxic and cobalt chloride-induced hypoxic environment in HeLa cells. Moreover. Chromatin-modifying protein 4A could increase the expression of hypoxia-inducible factor-1 alpha protein under normoxic condition, and enhance the transcription level of adenylate kinase 3, which is one of the target genes of hypoxia-inducible factor-1.
Significance: The functional screening platform therefore can be applied for the high-throughput screening of hypoxia-inducible factor-1-related genes, which would provide new insights into underlying molecular mechanisms that may regulate hypoxia in mammalian cells. (C) 2010 Elsevier Inc. All rights reserved.
|项目编号||2006AA02A305 ; 30700732 ; 2009ZX09503-004|
|资助机构||National High-tech R& ; D Program of China ; National Natural Science Foundation of China ; Key National ST Program|
|作者单位||1.Chinese Natl Human Genome Ctr, Beijing 100176, Peoples R China|
2.Peking Univ, Hlth Sci Ctr, Lab Med Immunol, Sch Basic Med Sci, Beijing 100191, Peoples R China
3.Peking Univ, Ctr Human Dis Genom, Beijing 100191, Peoples R China
4.So Med Univ, Inst Gene Engn, Guangzhou 510515, Guangdong, Peoples R China
|Shi, Taiping,Dong, Yunqiao,Li, Jing,et al. High-throughput screening identifies CHMP4A associated with hypoxia-inducible factor 1[J]. LIFE SCIENCES,2010,87(19-22):604-608.|
|APA||Shi, Taiping,Dong, Yunqiao,Li, Jing,Gao, Peng,Fu, Dongxu,&Ma, Dalong.(2010).High-throughput screening identifies CHMP4A associated with hypoxia-inducible factor 1.LIFE SCIENCES,87(19-22),604-608.|
|MLA||Shi, Taiping,et al."High-throughput screening identifies CHMP4A associated with hypoxia-inducible factor 1".LIFE SCIENCES 87.19-22(2010):604-608.|
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