The regulatory mechanism analysis of the constriction "velocity" at the contractile ring during mitosis

• Project/Area Number: 18K14703
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Aichi Medical University
• Principal Investigator: Hyodo Toshinori 愛知医科大学, 医学部, 講師 (40710645)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 細胞分裂 / 細胞質分裂 / キナーゼ / リン酸化

Outline of Final Research Achievements

Previously, we performed a screening to find novel candidates which relate the mitosis, thereby we found LUZP1. In this study, we showed that LUZP1 localizes at the centromere and the central spindle, and its localization require C terminal region of LUZP1. In addition, we found that LUZP1 interacts with both Kinase X and its Substrate Y. Our kinase assay indicates that LUZP1 prevent the phosphorylation of Substrate Y by Kinase X, however it also suggests that the interaction between LUZP1 and Kinase X induces Substrate Y phosphorylation in reverse. The above findings suggest a possibility that LUZP1 regulates the constriction velocity at the contractile ring during mitosis by preventing phosphorylation of Substrate Y by Kinase X. The function of LUZP1 during mitosis has not been reported. Our findings contribute to advances the elucidation of mitosis mechanisms.

Academic Significance and Societal Importance of the Research Achievements

全ての細胞は分裂で増殖を行う。これはがん細胞や病原菌もそうである。つまり分裂を完全に制御し、これらの増殖を制御できれば、人類はがんや感染症を克服できる可能性がある。しかし分裂の制御機構にはまだ不明な点が多く残っており、分裂の完全制御を成すためには、より詳細な細胞分裂機構の解明が必要になっている。そこでこれまでに申請者は細胞分裂に関与する新規因子の探索とその解析を行ってきた。本研究課題で申請者は細胞分裂に関わる新たな因子とその一部機能を明らかにした。分裂の完全制御にはまだ長い道のりが必要であるが、本研究はそれを成すための一歩になったといえる。

Research Products

• [Journal Article] Correction of a CD55 mutation to quantify the efficiency of targeted knock-in via flow cytometry (2022)
  • Author(s): Rahman Md. Lutfur、Hyodo Toshinori、Hasan Muhammad Nazmul、Mihara Yuko、Karnan Sivasundaram、Ota Akinobu、Tsuzuki Shinobu、Hosokawa Yoshitaka、Konishi Hiroyuki
  • Journal Title: Molecular Biology Reports Volume: - Issue: 7 Pages: 6241-6248
  • DOI: 10.1007/s11033-022-07422-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PBK Enhances Cellular Proliferation With Histone H3 Phosphorylation and Suppresses Migration and Invasion With CDH1 Stabilization in Colorectal Cancer (2022)
  • Author(s): Koshino Akira、Nagano Aya、Ota Akinobu、Hyodo Toshinori、Ueki Akane、Komura Masayuki、Sugimura-Nagata Akane、Ebi Masahide、Ogasawara Naotaka、Kasai Kenji、Hosokawa Yoshitaka、Kasugai Kunio、Takahashi Satoru、Inaguma Shingo
  • Journal Title: Frontiers in Pharmacology Volume: 12 Pages: 772926-772935
  • DOI: 10.3389/fphar.2021.772926
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Flow cytometry-based quantification of targeted knock-in events in human cell lines using a GPI-anchor biosynthesis gene <i>PIGP</i> (2021)
  • Author(s): Rahman Md.?Lutfur、Hyodo Toshinori、Hasan Muhammad?Nazmul、Mihara Yuko、Karnan Sivasundaram、Ota Akinobu、Tsuzuki Shinobu、Hosokawa Yoshitaka、Konishi Hiroyuki
  • Journal Title: Bioscience Reports Volume: 41 Issue: 12
  • DOI: 10.1042/bsr20212231
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Experimental strategies to achieve efficient targeted knock-in via tandem paired nicking (2021)
  • Author(s): Rahman Md. Lutfur、Hyodo Toshinori、Karnan Sivasundaram、Ota Akinobu、Hasan Muhammad Nazmul、Mihara Yuko、Wahiduzzaman Md、Tsuzuki Shinobu、Hosokawa Yoshitaka、Konishi Hiroyuki
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 1-13
  • DOI: 10.1038/s41598-021-01978-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD52 is a novel target for the treatment of FLT3-ITD-mutated myeloid leukemia (2021)
  • Author(s): Karnan Sivasundaram、Hanamura Ichiro、Uchino Kaori、Murakami Satsuki、Wahiduzzaman Md、Quang Vu Lam、Rahman Md Lutfur、Hasan Muhammad Nazmul、Hyodo Toshinori、Konishi Hiroyuki、Tsuzuki Shinobu、Yoshikawa Kazuhiro、Suzuki Susumu、Ueda Ryuzo、Ejiri Masayuki、Hosokawa Yoshitaka、Takami Akiyoshi
  • Journal Title: Cell Death Discovery Volume: 7 Issue: 1 Pages: 1-10
  • DOI: 10.1038/s41420-021-00446-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bi-allelic loss of FAM46C triggers tumor growth with concomitant activation of Akt signaling in multiple myeloma cells (2020)
  • Author(s): Kanasugi J, Hanamura I, Ota A, Karnan S, Vu LQ, Mizuno S, Wahiduzzaman M, Rahman ML, Hyodo T, Konishi H, Tsuzuki S, Hosokawa Y, Takami A
  • Journal Title: Cancer Science Volume: - Issue: 5 Pages: 999-999
  • DOI: 10.1111/cas.14386
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Discovery of novel molecular characteristics and cellular biological properties in ameloblastoma (2020)
  • Author(s): Kondo Sayuri、Ota Akinobu、Ono Takayuki、Karnan Sivasundaram、Wahiduzzaman Md、Hyodo Toshinori、Lutfur Rahman Md、Ito Kunihiro、Furuhashi Akifumi、Hayashi Tomio、Konishi Hiroyuki、Tsuzuki Shinobu、Hosokawa Yoshitaka、Kazaoka Yoshiaki
  • Journal Title: Cancer Medicine Volume: 9 Issue: 8 Pages: 2904-2917
  • DOI: 10.1002/cam4.2931
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tandem paired nicking promotes precise genome editing with scarce interference by p53 (2019)
  • Author(s): Hyodo T, Rahman ML, Karnan S, Ito T, Toyoda A, Ota A, Wahiduzzaman M, Tsuzuki S, Okada Y, Hosokawa Y, Konishi H.
  • Journal Title: Cell Rep. Volume: 30 Issue: 4 Pages: 1195-1207
  • DOI: 10.1016/j.celrep.2019.12.064
  • Peer Reviewed / Open Access
• [Presentation] CRISPR/Cas9 nickaseによるノックインはp53を活性化しない (2019)
  • Author(s): 兵頭 寿典、Md Lutfur Rahman、Karnan Sivasundaram、太田 明伸、都築 忍、細川 好孝、小西 裕之
  • Organizer: 第4回日本ゲノム編集学会
• [Presentation] CRISPR/Cas9 nickaseによるノックインはp53を活性化しない (2019)
  • Author(s): 兵頭 寿典、Rahman Md. Lutfur、Sivasundaram Karnan、太田 明伸、都築 忍、細川 好孝、小西 裕之
  • Organizer: ゲノム編集学会
• [Remarks] 愛知医科大学 生化学講座
  • URL: https://www.aichi-med-u.ac.jp/su06/su0607/su060702/03.html#iLink04
• [Remarks] DNAの２本鎖切断を起こさない安全で正確なゲノム編集法に関する研究成果について
  • URL: https://www.aichi-med-u.ac.jp/su03/su03_2020/su03_2020_01/1210815_5196.html
• [Remarks] DNAの２本鎖切断を起こさないゲノム編集方法 ～安全なゲノム編集治療への応用に期待～
  • URL: https://www.nig.ac.jp/nig/ja/2020/01/research-highlights_ja/pr20200129.html
• [Remarks] DNAの２本鎖切断を起こさないゲノム編集方法
  • URL: https://www.genome-sci.jp/research_results#2
• [Remarks] 教員紹介
  • URL: https://www.aichi-med-u.ac.jp/data/profile/Staff_0281.html