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Title of Journal: Angiogenesis

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Abbravation: Angiogenesis

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Springer Netherlands

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DOI

10.1007/s11608-007-0116-2

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1573-7209

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Protein kinase D2 and heat shock protein 90 beta a

Authors: Daisuke Miwa Tomohisa Sakaue Hirofumi Inoue Nobuaki Takemori Maki Kurokawa Shinji Fukuda Kazuya Omi Katsutoshi Goishi Shigeki Higashiyama
Publish Date: 2013/03/21
Volume: 16, Issue: 3, Pages: 675-688
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Abstract

Vascular endothelial growth factor VEGF is a major angiogenic factor that activates proangiogenic molecules to generate new vessels Recently we identified a VEGFAinduced proangiogenic gene BCL6 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 VEGFA stimulation A luciferase reporter assay showed that the promoter activity of the BAZF gene was unchanged by VEGFA stimulation However we found that the stability of BAZF mRNA increased in a VEGFA/PRKD2dependent 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 VEGFA/PRKD2 activation These data suggest that HSP90β may positively regulate angiogenesis not only as a protein chaperone but also as an mRNA stabilizer for proangiogenic genes such as BAZF in a PRKD2 activitydependent mannerWe would like to thank Drs Yoshimura Keio University Nishimura Kumamoto University and Miyoshi RIKEN BioResource Center for kindly providing the plasmids used in this study We gratefully appreciate discussions with Drs Matsushita Ohnuki and Nakayama of Ehime University This study was supported by a grant from Ehime University DM 054402060 and a GrantinAid for Scientific Research 23112513 to S Higashiyama 22590501 to H Inoue from the Ministry of Education Culture Sports Science and Technology Japan

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