| First Author | Widau RC | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 21 | Pages | 4270-82 |
| PubMed ID | 22907756 | Mgi Jnum | J:189250 |
| Mgi Id | MGI:5444799 | Doi | 10.1128/MCB.06424-11 |
| Citation | Widau RC, et al. (2012) p19Arf Represses Platelet-Derived Growth Factor Receptor beta by Transcriptional and Posttranscriptional Mechanisms. Mol Cell Biol 32(21):4270-82 |
| abstractText | In addition to cancer surveillance, p19(Arf) plays an essential role in blocking signals stemming from platelet-derived growth factor receptor beta (Pdgfrbeta) during eye development, but the underlying mechanisms have not been clear. We now show that without Arf, pericyte hyperplasia in the eye results from enhanced Pdgfrbeta-dependent proliferation from embryonic day 13.5 (E13.5) of mouse development. Loss of Arf in the eye increases Pdgfrbeta expression. In cultured fibroblasts and pericyte-like cells, ectopic p19(Arf) represses and Arf knockdown enhances the expression of Pdgfrbeta mRNA and protein. Ectopic Arf also represses primary Pdgfrbeta transcripts and a plasmid driven by a minimal promoter, including one missing the CCAAT element required for high-level expression. p19(Arf) uses both p53-dependent and -independent mechanisms to control Pdgfrbeta. In vivo, without p53, Pdgfrbeta mRNA is elevated and eye development abnormalities resemble the Arf (-/-) phenotype. However, effects of p53 on Pdgfrbeta mRNA do not appear to be due to direct p53 or RNA polymerase II recruitment to the promoter. Although p19(Arf) controls Pdgfrbeta mRNA in a p53-dependent manner, it also blunts Pdgfrbeta protein expression by blocking new protein synthesis in the absence of p53. Thus, our findings demonstrate a novel capacity for p19(Arf) to control Pdgfrbeta expression by p53-dependent and -independent mechanisms involving RNA transcription and protein synthesis, respectively, to promote the vascular remodeling needed for normal vision. |
