| First Author | Xiao W | Year | 2009 |
| Journal | Cancer Res | Volume | 69 |
| Issue | 6 | Pages | 2599-606 |
| PubMed ID | 19258512 | Mgi Jnum | J:147093 |
| Mgi Id | MGI:3839213 | Doi | 10.1158/0008-5472.CAN-08-2595 |
| Citation | Xiao W, et al. (2009) U19/Eaf2 binds to and stabilizes von hippel-lindau protein. Cancer Res 69(6):2599-606 |
| abstractText | 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 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 1alpha (HIF1alpha), 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 HIF1alpha and angiogenesis, possibly via direct binding and stabilization of pVHL. |
