RRC ID 48812
Author Miwa D, Sakaue T, Inoue H, Takemori N, Kurokawa M, Fukuda S, Omi K, Goishi K, Higashiyama S.
Title Protein kinase D2 and heat shock protein 90 beta are required for BCL6-associated zinc finger protein mRNA stabilization induced by vascular endothelial growth factor-A.
Journal Angiogenesis
Abstract Vascular endothelial growth factor (VEGF) is a major angiogenic factor that activates pro-angiogenic molecules to generate new vessels. Recently, we identified a VEGF-A-induced pro-angiogenic gene, BCL-6 associated zinc finger protein (BAZF), in endothelial cells. BAZF interacts with CBF1, a transcriptional regulator of Notch signaling, and downregulates Notch signaling by inducing the degradation of CBF1. A signal inhibition assay with a combination of chemical inhibitors and siRNA revealed that the protein kinase D (PRKD) family, mainly PRKD2, mediated BAZF gene expression by VEGF-A stimulation. A luciferase reporter assay showed that the promoter activity of the BAZF gene was unchanged by VEGF-A stimulation. However, we found that the stability of BAZF mRNA increased in a VEGF-A/PRKD2-dependent manner. In further studies to investigate the underlying mechanism, we successfully identified heat shock protein 90 beta (HSP90β) as a molecule that interacts with and stabilizes BAZF mRNA following VEGF-A/PRKD2 activation. These data suggest that HSP90β may positively regulate angiogenesis, not only as a protein chaperone, but also as an mRNA stabilizer for pro-angiogenic genes, such as BAZF, in a PRKD2 activity-dependent manner.
Volume 16(3)
Pages 675-88
Published 2013-7-1
DOI 10.1007/s10456-013-9345-x
PMID 23515950
MeSH Blotting, Western Electrophoresis, Gel, Two-Dimensional Gene Expression Regulation / physiology* HSP90 Heat-Shock Proteins / metabolism* Human Umbilical Vein Endothelial Cells Humans Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism Luciferases Protein Kinase C / metabolism Protein Kinase D2 Protein Kinases / metabolism* RNA Interference RNA Stability / drug effects RNA Stability / physiology* Real-Time Polymerase Chain Reaction Receptors, Notch / metabolism Repressor Proteins / metabolism Repressor Proteins / physiology* Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / drug effects Vascular Endothelial Growth Factor A / pharmacology
IF 9.78
Times Cited 11
DNA material CSII-CMV-MCS-IRES2-Bsd (RDB04385)