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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.

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.

journal_name

Angiogenesis

journal_title

Angiogenesis

authors

Miwa D,Sakaue T,Inoue H,Takemori N,Kurokawa M,Fukuda S,Omi K,Goishi K,Higashiyama S

doi

10.1007/s10456-013-9345-x

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

675-88

issue

3

eissn

0969-6970

issn

1573-7209

journal_volume

16

pub_type

杂志文章

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