Mitosis regulation by Apollon

• Project/Area Number: 25460084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Naito Mikihiko 国立医薬品食品衛生研究所, 遺伝子医薬部, 部長 (00198011)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: サイクリンA / Apollon / 細胞周期 / ユビキチン / UBCドメイン / 細胞分裂 / サイクリン

Outline of Final Research Achievements

During mitosis, cyclin A and cyclin B are ubiquitylated by the anaphase promoting complex/cyclosome (APC/C) and then subjected to proteasomal degradation. However, cyclin A, but not cyclin B, begins to be degraded in the prometaphase when APC/C is inactivated by the spindle assembly checkpoint (SAC). Here we show that Apollon (also known as BRUCE or BIRC6) plays a role in SAC-independent degradation of cyclin A in early mitosis. Apollon interacts with cyclin A and facilitates cyclin A ubiquitylation. In Apollon-deficient cells, mitotic degradation of cyclin A is delayed, and total but not CDK-bound cyclin A level was increased. We propose Apollon to be a novel regulator of mitotic cyclin A degradation independent on SAC.

Research Products

• [Journal Article] Degradation of Stop Codon Read-through Mutant Proteins via the Ubiquitin-Proteasome System Causes Hereditary Disorders. (2015)
  • Author(s): Shibata N, Ohoka N, Sugaki Y, Onodera C, Inoue M, Sakuraba Y, Takakura D, Hashii N, Kawasaki N, Gondo Y, Naito M
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 47 Pages: 28428-28437
  • DOI: 10.1074/jbc.m115.670901
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Apollon/Bruce is upregulated by Humanin. (2014)
  • Author(s): 4.Hashimoto, Y., Takeshita, Y., Naito, M., Uchino, H. and Matsuoka, M
  • Journal Title: Mol Cell Biochem. Volume: 397 Issue: 1-2 Pages: 147-55
  • DOI: 10.1007/s11010-014-2182-4
  • Peer Reviewed / Open Access
• [Journal Article] Apollon protein promotes early mitotic Cyclin A degradation independent of the spindle assembly checkpoint. (2014)
  • Author(s): Kikuchi, R., Ohata, H., Ohoka, N., Kawabata, A., Naito, M.
  • Journal Title: The Journal of Biological Chemistry Volume: 289 Issue: 6 Pages: 3457-3467
  • DOI: 10.1074/jbc.m113.514430
  • Peer Reviewed
• [Journal Article] Design and synthesis of tamoxifen derivatives as a selective estrogen receptor down-regulator. (2014)
  • Author(s): Shoda, T., Okuhira, K., Kato, M., Demizu, Y., Inoue, H., Naito, M., and Kurihara, M.
  • Journal Title: Bioorg Med Chem Lett Volume: 24 Issue: 1 Pages: 87-89
  • DOI: 10.1016/j.bmcl.2013.11.078
  • Peer Reviewed
• [Journal Article] Development of hybrid small molecules that induce degradation of estrogen receptor-alpha and necrotic cell death in breast cancer cells. (2013)
  • Author(s): Okuhira, K., Demizu, Y., Hattori, T., Ohoka, N., Shibata, N., Nishimaki-Mogami, T., Okuda, H., Kurihara, M., Natiro, M.
  • Journal Title: Cancer Science Volume: 104 Issue: 11 Pages: 1492-1498
  • DOI: 10.1111/cas.12272
  • Peer Reviewed
• [Presentation] Protein knockdown by SNIPER compounds: Application for basic research and cancer therapy (2016)
  • Author(s): Naito M, Hattori T, Ohoka N, Shibata N, Shoda T, Demizu Y, Kurihara M
  • Organizer: 第１０回日米がん合同会議
  • Place of Presentation: ラハイナ
  • Year and Date: 2016-02-16
  • Int'l Joint Research
• [Presentation] Protein knockdown by SNIPER compounds, inducers for target protein-selective degradation (2015)
  • Author(s): Naito M
  • Organizer: The 20th 国際化学療法シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2015-12-09
  • Int'l Joint Research / Invited
• [Presentation] Degradation of C-terminally extended proteins by stop codon read-through mutations cause hereditary disorders (2015)
  • Author(s): Shibata N, Ohoka N, Gondo Y, Naito M
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] TACC3分解誘導剤によるがん細胞のユビキチン関連死 (2015)
  • Author(s): 大岡伸通、柴田識人、服部隆行、内藤幹彦
  • Organizer: 第19回日本がん分子標的治療学会 学術集会
  • Place of Presentation: 松山
  • Year and Date: 2015-06-10
• [Presentation] Apollon細胞分裂初期においてスピンドルチェックポイント非依存的なcyclin Aの分解を促進する (2014)
  • Author(s): 大岡 伸通，内藤 幹彦
  • Organizer: 日本がん分子標的治療学会第18回学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2014-06-25 – 2014-06-27
• [Presentation] Apollon binds cyclin A and promotes degradation in early mitosis independent of spindle assembly checkpoint (2014)
  • Author(s): Ohoka N, Ohata H, Naito M.
  • Organizer: Keystone Symposia on Molecular and Cellular Biology, The Ubiquitin System: From Basic Science to Drug Discovery
  • Place of Presentation: Bigsky
• [Presentation] Apollon細胞分裂初期においてスピンドルチェックポイント非依存的なcyclin Aの分解を促進する (2014)
  • Author(s): 大岡 伸通，大畑 広和，内藤 幹彦
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] Apollon binds cyclin A and promotes degradation in early mitosis independent of spindle assembly checkpoint (2013)
  • Author(s): 大岡 伸通，大畑 広和，内藤 幹彦
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Remarks] 国立医薬品食品衛生研究所 遺伝子医薬部ホームページ
  • URL: http://www.nihs.go.jp/mtgt/index.html
• [Remarks] 国立医薬品食品衛生研究所遺伝子医薬部ホームページ
  • URL: http://www.nihs.go.jp/mtgt/index.html
• [Remarks] 国立医薬品食品衛生研究所 機能生化学部ホームページ
  • URL: http://www.nihs.go.jp/dfbg/frame.html