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U19/Eaf2 Binds to and Stabilizes von Hippel-Lindau Protein
Xiao, Wuhan; Ai, Junkui; Habermacher, Geoffrey; Volpert, Olga; Yang, Ximing; Zhang, Ai-yuan; Hahn, Junghyun; Cai, Xiaoyan; Wang, Zhou; Wang, Z, Univ Pittsburgh, Coll Med, Dept Urol, Suite G40,5200 Ctr Ave, Pittsburgh, PA 15232 USA
2009
Source PublicationCANCER RESEARCH
Volume69Issue:6Pages:2599-2606
AbstractStudies 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]
KeywordTumor-suppressor Protein Cell-proliferation Ubiquitin Ligase Renal-carcinoma Vascular Tumors Hif-alpha Vhl Gene Complex Cancer Inactivation
Department[Wang, Zhou] Univ Pittsburgh, Coll Med, Dept Urol, Pittsburgh, PA 15232 USA; [Wang, Zhou] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA; [Yang, Ximing] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA; [Habermacher, Geoffrey; Volpert, Olga; Hahn, Junghyun; Cai, Xiaoyan; Wang, Zhou] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA; [Wang, Zhou] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA; [Xiao, Wuhan] Chinese Acad Sci, Inst Hydrobiol, Wuhan, Peoples R China
Subject AreaOncology
Funding OrganizationNIH [R37 DK51193, R01 CA120386, P50 CA90386]; Mellam Family Foundation ; NIH [R37 DK51193, R01 CA120386, P50 CA90386]; Mellam Family Foundation ; NIH [R37 DK51193, R01 CA120386, P50 CA90386]; Mellam Family Foundation ; NIH [R37 DK51193, R01 CA120386, P50 CA90386]; Mellam Family Foundation
Indexed BySCI
Language英语
WOS IDWOS:000264541300055
Funding OrganizationNIH [R37 DK51193, R01 CA120386, P50 CA90386]; Mellam Family Foundation ; NIH [R37 DK51193, R01 CA120386, P50 CA90386]; Mellam Family Foundation ; NIH [R37 DK51193, R01 CA120386, P50 CA90386]; Mellam Family Foundation ; NIH [R37 DK51193, R01 CA120386, P50 CA90386]; Mellam Family Foundation
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Cited Times:24[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/152342/7810
Collection期刊论文
Corresponding AuthorWang, Z, Univ Pittsburgh, Coll Med, Dept Urol, Suite G40,5200 Ctr Ave, Pittsburgh, PA 15232 USA
Recommended Citation
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, Z, Univ Pittsburgh, Coll Med, Dept Urol, Suite G40,5200 Ctr Ave, Pittsburgh, PA 15232 USA.(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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