title: AUF1/hnRNP D represses expression of VEGF in macrophages.
abstract: 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.
authors.affiliation: Veterans Administration Research Service, White River Junction, VT 05009, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Fellows
authors.forename: Mary E
authors.initials: ME
authors.lastname: Griffin
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Petrella
authors.forename: Lihui
authors.initials: L
authors.lastname: Zhong
authors.forename: Fatemeh P
authors.initials: FP
authors.lastname: Parvin-Nejad
authors.forename: Roy
authors.initials: R
authors.lastname: Fava
authors.forename: Peter
authors.initials: P
authors.lastname: Morganelli
authors.forename: R Brooks
authors.initials: RB
authors.lastname: Robey
authors.forename: Ralph C
authors.initials: RC
authors.lastname: Nichols
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001854:Bone Marrow Cells; D005786:Gene Expression Regulation; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000096:biosynthesis / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D010455:Peptides; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse