| U19/Eaf2 Binds to and Stabilizes von Hippel-Lindau Protein | |
| Xiao, Wuhan6; Ai, Junkui; Habermacher, Geoffrey4; Volpert, Olga4; Yang, Ximing3; Zhang, Ai-yuan; Hahn, Junghyun4; Cai, Xiaoyan4; Wang, Zhou1,2,4,5 | |
| 刊名 | CANCER RESEARCH
 |
| 2009-03-15 | |
| 卷号 | 69期号:6页码:2599-2606 |
| 关键词 | TUMOR-SUPPRESSOR PROTEIN CELL-PROLIFERATION UBIQUITIN LIGASE RENAL-CARCINOMA VASCULAR TUMORS HIF-ALPHA VHL GENE COMPLEX CANCER INACTIVATION |
| ISSN号 | 0008-5472 |
| 通讯作者 | Wang, Z, Univ Pittsburgh, Coll Med, Dept Urol, Suite G40,5200 Ctr Ave, Pittsburgh, PA 15232 USA |
| 中文摘要 | Studies have firmly established a key regulatory role for the tumor suppressor pVHL in the regulation of the vascular system and normal spermatogenesis. Here, we report that knockout of the newly identified tumor suppressor U19/Eaf2 also caused vascular system abnormalities and aspermatogenesis, suggesting a potential link between U19/Eaf2 and pVHL. Coimmunoprecipitation and in vitro binding assays showed an association between U19/Eaf2 and pVHL, whereas deletion mutagenesis revealed the requirement of the NH2 terminus of U19/Eaf2 and both the alpha and beta domains of pVHL for this binding. U19/Eaf2 stabilizes pVHL, as shown by protein stability and pulse-chase studies. Testes and mouse embryonic fibroblasts (MEF) derived from U19/Eaf2 knockout mice expressed reduced levels of pVHL, indicating that full in vivo expression of pVHL indeed requires U19/Eaf2. As expected, U19/Eaf2 knockout MEF cells exhibited an increased level and activity of hypoxia-inducible factor 1 alpha (HIF1 alpha), a protein typically regulated via a pVHL-mediated degradation pathway. Furthermore, angiogenesis in a Matrigel plug assay was significantly increased in U19/Eaf2 knockout mice. The above observations argue that U19/Eaf2 can modulate HIF1 alpha and angiogenesis, possibly via direct binding and stabilization of pVHL. [Cancer Res 2009;69(6):2599-606] |
| 英文摘要 | Studies have firmly established a key regulatory role for the tumor suppressor pVHL in the regulation of the vascular system and normal spermatogenesis. Here, we report that knockout of the newly identified tumor suppressor U19/Eaf2 also caused vascular system abnormalities and aspermatogenesis, suggesting a potential link between U19/Eaf2 and pVHL. Coimmunoprecipitation and in vitro binding assays showed an association between U19/Eaf2 and pVHL, whereas deletion mutagenesis revealed the requirement of the NH2 terminus of U19/Eaf2 and both the alpha and beta domains of pVHL for this binding. U19/Eaf2 stabilizes pVHL, as shown by protein stability and pulse-chase studies. Testes and mouse embryonic fibroblasts (MEF) derived from U19/Eaf2 knockout mice expressed reduced levels of pVHL, indicating that full in vivo expression of pVHL indeed requires U19/Eaf2. As expected, U19/Eaf2 knockout MEF cells exhibited an increased level and activity of hypoxia-inducible factor 1 alpha (HIF1 alpha), a protein typically regulated via a pVHL-mediated degradation pathway. Furthermore, angiogenesis in a Matrigel plug assay was significantly increased in U19/Eaf2 knockout mice. The above observations argue that U19/Eaf2 can modulate HIF1 alpha and angiogenesis, possibly via direct binding and stabilization of pVHL. [Cancer Res 2009;69(6):2599-606] |
| 学科主题 | Oncology |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 类目[WOS] | Oncology |
| 研究领域[WOS] | Oncology |
| 关键词[WOS] | TUMOR-SUPPRESSOR PROTEIN ; CELL-PROLIFERATION ; UBIQUITIN LIGASE ; RENAL-CARCINOMA ; VASCULAR TUMORS ; HIF-ALPHA ; VHL GENE ; COMPLEX ; CANCER ; INACTIVATION |
| 收录类别 | SCI |
| 资助信息 | NIH [R37 DK51193, R01 CA120386, P50 CA90386]; Mellam Family Foundation |
| 语种 | 英语 |
| WOS记录号 | WOS:000264541300055 |
| 公开日期 | 2010-10-13 |
| 内容类型 | 期刊论文 |
| 源URL | [http://ir.ihb.ac.cn/handle/152342/7810]  |
| 专题 | 水生生物研究所_中科院水生所知识产出（2009年前）_期刊论文 |
| 作者单位 | 1.Univ Pittsburgh, Coll Med, Dept Urol, Pittsburgh, PA 15232 USA 2.Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA 3.Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA 4.Northwestern Univ, Dept Urol, Chicago, IL 60611 USA 5.Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA 6.Chinese Acad Sci, Inst Hydrobiol, Wuhan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xiao, Wuhan,Ai, Junkui,Habermacher, Geoffrey,et al. U19/Eaf2 Binds to and Stabilizes von Hippel-Lindau Protein[J]. CANCER RESEARCH,2009,69(6):2599-2606. |
| APA | Xiao, Wuhan.,Ai, Junkui.,Habermacher, Geoffrey.,Volpert, Olga.,Yang, Ximing.,...&Wang, Zhou.(2009).U19/Eaf2 Binds to and Stabilizes von Hippel-Lindau Protein.CANCER RESEARCH,69(6),2599-2606. |
| MLA | Xiao, Wuhan,et al."U19/Eaf2 Binds to and Stabilizes von Hippel-Lindau Protein".CANCER RESEARCH 69.6(2009):2599-2606. |
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