最先端研究セミナー

講演者：　東山　繁樹　（教授、愛媛大学プロテオサイエンスセンター　細胞増殖・腫瘍制御部門）

Title: CUL3-based Ub E3 ligase; a key modulator in vascular endothelial cell function and angiogenesis

Abstract:

Angiogenesis is the process of new microvascular formation from pre-existing vessels. In adult, homeostasis of angiogenesis is maintained on the balance between pro- and anti-angiogenic signaling. “Out of the balance” causes abnormal angiogenesis, which is linked to more than 70 diseases, affecting ~1 billion people, such as cancer, diabetic blindness, age-related macular degeneration, rheumatoid arthritis, psoriasis, etc. in excessive angiogenesis, and coronary artery disease, stroke, and chronic wounds, etc. in insufficient angiogenesis. Therefore, it is crucial to understand the molecular mechanism underlining “balancing between pro- and anti-angiogenic signaling” for establishing novel therapeutic strategies. We recently identified a Cullin 3 (CUL3)-based ubiquitin (Ub) ligase complex, CUL3-BAZF-CBF1, which is a key player to break the balance between VEGF (pro-angiogenic) and Notch (anti-angiogenic) signaling. In this seminar, I will present the multiple roles of CUL3-besed Ub ligase complexes in endothelial cells and angiogenesis, and our technical approaches based on a 20K protein array originally made in our center.

References:

1. Ohnuki H, Inoue H, Takemori N, Nakayama H, Sakaue T, Fukuda S, Miwa D, Nishiwaki E, Hatano M, Tokuhisa T, Endo Y, Nose M, Higashiyama S. BAZF, a novel component of cullin3-based E3 ligase complex, mediates VEGFR and Notch cross-signaling in angiogenesis. Blood 119, 2688-98, 2012.
2. Sakaue T, Sakakibara I, Uesugi T, Fujisaki A, Nakashiro KI, Hamakawa H, Kubota E, Joh T, Imai YK, Izutani H, Higashiyama S. The CUL3-SPOP-DAXX axis is a novel regulator of VEGFR2 expression in vascular endothelial cells. Sci Rep. 7, 42845, 2017.
3. Maekawa M, Tanigawa K, Sakaue T, Hiyoshi H, Kubota E, Joh T, Watanabe Y, Taguchi T, Higashiyama S. Cullin-3 and its adaptor protein ANKFY1 determine the surface level of integrin β1 in endothelial cells. Biol Open. 6, 1707-1719,
4. Kovačević I, Sakaue T, Majoleé J, Pronk MC, Maekawa M, Geerts D, Fernandez-Borja M, Higashiyama S, Hordijk PL. The Cullin-3-Rbx1-KCTD10 complex controls endothelial barrier function via K63 ubiquitination of RhoB. J Cell Biol. 217, 1015-1032. 2018.

担当分野：　分子血管制御分野　南（内線：6500）

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