U19/Eaf2 binds to and stabilizes von hippel-lindau protein

Wuhan Xiao, Junkui Ai, Geoffrey Habermacher, Olga Volpert, Ximing Yang, Ai Yuan Zhang, Junghyun Hahn, Xiaoyan Cai, Zhou Wang*

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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 NH 2 terminus of U19/Eaf2 and both the α and β 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/Eqf2 knockout mice expressed reduced levels of pYHL, 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 1α (HIF1α), 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 HIF1α and angiogenesis, possibly via direct binding and stabilization Of pVHL.

Original languageEnglish (US)
Pages (from-to)2599-2606
Number of pages8
JournalCancer Research
Volume69
Issue number6
DOIs
StatePublished - Mar 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Xiao, W., Ai, J., Habermacher, G., Volpert, O., Yang, X., Zhang, A. Y., Hahn, J., Cai, X., & Wang, Z. (2009). U19/Eaf2 binds to and stabilizes von hippel-lindau protein. Cancer Research, 69(6), 2599-2606. https://doi.org/10.1158/0008-5472.CAN-08-2595