Seminar

Seminar

Light and dark sides of polarity proteins

Title Light and dark sides of polarity proteins
Lecturer 中山 雅敬 博士 (Max-Planck-Institute for Heart and Lung Research )
Language English
Date&Time 07/24/2017 (Mon) 11:00~12:00
Venue 大セミナー室
Detail Cell proliferation is controlled not only by growth factors, but also by polarization. Disrupted polarity is a hallmark of excessive cell expansion, however a molecular mechanism remains elusive. Polarity protein atypical protein kinase C lambda/iota (aPKC l), is associated with proliferation and is an oncogene. In endothelia, suppression of aPKC l impairs proliferation despite hyper-activated vascular endothelial growth factor (VEGF) signaling (1, 2). Here we show that aPKC l phosphorylates the DNA binding domain of forkhead box O1 (FoxO1) transcription factor, a gatekeeper of endothelial growth. Although VEGF signaling is known to exclude FoxO1 from the nucleus, consequently increasing c-Myc abundance and proliferation, aPKC l controls c-Myc transcription via FoxO1 without affecting its localization in vivo. We find this pathway is strongly activated in the malignant vascular sarcoma, angiosarcoma, and aPKC inhibition reduces c-Myc expression and proliferation of angiosarcoma cells. Additionally, we confirm phosphorylation of FoxO1 by aPKC in more than 70% of the angiosarcoma patients. While median survival time of phospho-FoxO1 positive patients is 14 months, that of negative patients is 37 months. Our findings may provide a new therapeutic strategy for treatment of malignant cancers, such as angiosarcoma.
Contact 神経システム生物学
稲垣 直之 (ninagaki@bs.naist.jp)

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