Regulation of Ephrin receptor by inducible ubiquitin ligase SSB

• Project/Area Number: 15K21056
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy; General medical chemistry
• Research Institution: Nagoya University
• Principal Investigator: Okumura Fumihiko 名古屋大学, 理学研究科, 講師 (00507212)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ユビキチン / EphB2 / 細胞間反発運動 / タンパク質分解 / SPSB4 / Eph / SSB

Outline of Final Research Achievements

We identified ephB2 receptor as SSB4 (SPSB4)-interacting protein. SPSB4 is a functionally unknown ubiquitin ligase.EphB2 is known to act as oncogene or tumuor suppressor depending on the cell type.
We showed that SPSB4 destabilized EphB2 cytoplasmic domain. Next, we analyzed cell repulsive responses by co-culturing ephrin B2-expressing cells and EphB2-expressing cells.As a result, SPSB4 knock down enhanced cell repulsive responses and SPSB4 was shown to prevent EphB2 signaling pathway.

Research Products

• [Journal Article] Ubiquitin ligase SPSB4 diminishes cell repulsive responses mediated by EphB2. (2017)
  • Author(s): 1.Okumura, F., Joo-Okumura, A., Obara, K., Petersen, A., Nishikimi, A., Fukui, Y., Nakatsukasa, K., and Kamura, T
  • Journal Title: Mol Biol Cell Volume: 28 Issue: 24 Pages: 3532-3541
  • DOI: 10.1091/mbc.e17-07-0450
  • Peer Reviewed / Open Access
• [Journal Article] Hypoxia-inducible factor-2α stabilizes the von Hippel-Lindau (VHL) disease suppressor, Myb-related protein 2. (2017)
  • Author(s): Okumura F, Joo-Okumura A, Nakatsukasa K, Kamura T.
  • Journal Title: PLoS One Volume: 12(4):e0175593. Issue: 4 Pages: 1-10
  • DOI: 10.1371/journal.pone.0175593
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ASB7 regulates spindle dynamics and genome integrity by targeting DDA3 for proteasomal degradation. (2016)
  • Author(s): Uematsu K, Okumura F, Tonogai S, Joo-Okumura A, Alemayehu DH, Nishikimi A, Fukui Y, Nakatsukasa K, Kamura T.
  • Journal Title: The Journal of Cell Biology Volume: 215(1) Pages: 95-106
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Parallel Regulation of von Hippel-Lindau Disease by pVHL-Mediated Degradation of B-Myb and Hypoxia-Inducible Factor α. (2016)
  • Author(s): Okumura F, Uematsu K, Byrne SD, Hirano M, Joo-Okumura A, Nishikimi A, Shuin T, Fukui Y, Nakatsukasa K, Kamura T.
  • Journal Title: Molecular Cellular Biology Volume: 36 Issue: 12 Pages: 1803-1817
  • DOI: 10.1128/mcb.00067-16
  • NAID: 120005844088
  • Peer Reviewed / Open Access
• [Journal Article] Parallel regulation of VHL disease by pVHL-mediated degradation of B-Myb and HIF-alpha (2016)
  • Author(s): Okumura, F., Uematsu, K., Byrne, S.D., Hirano, M., Okumura, A. J., Nishikimi, A., Shuin, T., Fukui, Y., Nakatsukasa, K. & Kamura, T.
  • Journal Title: Mol. Cell. Biol. Volume: N/A
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The role of cullin 5-containing ubiquitin ligases (2016)
  • Author(s): Okumura, F. , Joo-Okumura, A., Nakatsukasa, K. & Kamura, T.
  • Journal Title: Cell Division. Volume: N/A Issue: 1 Pages: 1-1
  • DOI: 10.1186/s13008-016-0016-3
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Proteolytic regulation of metabolic enzymes by E3 ubiquitin ligase complexes: lessons from yeast. (2015)
  • Author(s): Nakatsukasa, K., Okumura, F., Kamura, T
  • Journal Title: Crit Rev Biochem Mol Biol. Volume: 50 Issue: 6 Pages: 489-502
  • DOI: 10.3109/10409238.2015.1081869
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The ubiquitin ligase SCFUcc1 acts as a metabolic switch for the glyoxylate cycle. (2015)
  • Author(s): Nakatsukasa, K., Nishimura, T., Byrne, D., Okamoto, M., Takahashi-Nakaguchi, A., Chibana, H., Okumura, F., Kamura, T.
  • Journal Title: Molecular Cell Volume: 59 Issue: 1 Pages: 22-34
  • DOI: 10.1016/j.molcel.2015.04.013
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] pVHL 依存的なB-Myb とHIF αの分解はそれぞれ独立してVHL 病を制御している (2017)
  • Author(s): 奥村 文彦, 植松 桂司, Byrne STUART D., 平野 みえ, 奥村( 城尾) 晶子, 錦見 昭彦, 執印 太郎, 福井 宣規, 中務 邦雄, 嘉村 巧
  • Organizer: 日本薬学会第１３７年会
  • Place of Presentation: 東北大学
  • Year and Date: 2017-03-25
• [Presentation] ユビキチンリガーゼASB7によるDDA3の発現制御は適切な紡錘体形成と染色体分配に必要である (2016)
  • Author(s): 奥村 文彦, 植松 桂司, 外海 駿輔, 奥村（城尾） 晶子, Dawit Hailu Alemayehu, 錦見 昭彦, 福井 宣規, 中務 邦雄, 嘉村 巧
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-12-01
• [Presentation] pVHL依存的なFOBとHIFαの分解はそれぞれ独立してVHL病を制御している (2015)
  • Author(s): 1.奥村 文彦, 植松 桂司, Stuart D. Byrne, 平野 みえ, 奥村(城尾) 晶子, 錦見 昭彦, 執印 太郎, 福井 宣規, 中務 邦雄, 嘉村 巧
  • Organizer: 第38回 日本分子生物学会年会、第88回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-03
• [Remarks] 名古屋大学リポジトリ
  • URL: http://ir.nul.nagoya-u.ac.jp/jspui/
• [Remarks] 名古屋大学理学研究科論文紹介
  • URL: http://www.bio.nagoya-u.ac.jp/paper/
• [Remarks] 研究教育成果情報
  • URL: http://www.nagoya-u.ac.jp/about-nu/public-relations/researchinfo/index.html