| First Author | Fellows A | Year | 2012 |
| Journal | Mol Biol Cell | Volume | 23 |
| Issue | 8 | Pages | 1414-22 |
| PubMed ID | 22379108 | Mgi Jnum | J:197697 |
| Mgi Id | MGI:5494351 | Doi | 10.1091/mbc.E11-06-0545 |
| Citation | Fellows A, et al. (2012) AUF1/hnRNP D represses expression of VEGF in macrophages. Mol Biol Cell 23(8):1414-22 |
| abstractText | Vascular endothelial growth factor (VEGF) is a regulator of vascularization in development and is a key growth factor in tissue repair. In disease, VEGF contributes to vascularization of solid tumors and arthritic joints. This study examines the role of the mRNA-binding protein AUF1/heterogeneous nuclear ribonucleoprotein D (AUF1) in VEGF gene expression. We show that overexpression of AUF1 in mouse macrophage-like RAW-264.7 cells suppresses endogenous VEGF protein levels. To study 3' untranslated region (UTR)-mediated regulation, we introduced the 3' UTR of VEGF mRNA into a luciferase reporter gene. Coexpression of AUF1 represses VEGF-3' UTR reporter expression in RAW-264.7 cells and in mouse bone marrow-derived macrophages. The C-terminus of AUF1 contains arginine-glycine-glycine (RGG) repeat motifs that are dimethylated. Deletion of the RGG domain of AUF1 eliminated the repressive effects of AUF1. Surprisingly, expression of an AUF1-RGG peptide reduced endogenous VEGF protein levels and repressed VEGF-3' UTR reporter activity in RAW-264.7 cells. These findings demonstrate that AUF1 regulates VEGF expression, and this study identifies an RGG peptide that suppresses VEGF gene expression. |
