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Angiogenesis
Erschienen in: Angiogenesis 3/2013

01.07.2013 | Original Paper

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

verfasst von: Daisuke Miwa, Tomohisa Sakaue, Hirofumi Inoue, Nobuaki Takemori, Maki Kurokawa, Shinji Fukuda, Kazuya Omi, Katsutoshi Goishi, Shigeki Higashiyama

Erschienen in: Angiogenesis | Ausgabe 3/2013

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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.
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Metadaten
Titel
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
verfasst von
Daisuke Miwa
Tomohisa Sakaue
Hirofumi Inoue
Nobuaki Takemori
Maki Kurokawa
Shinji Fukuda
Kazuya Omi
Katsutoshi Goishi
Shigeki Higashiyama
Publikationsdatum
01.07.2013
Verlag
Springer Netherlands
Erschienen in
Angiogenesis / Ausgabe 3/2013
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-013-9345-x

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