Molecular mechanisms of neuronal cell death and chromosome segregation errors induced by defects in JSAP-mediated intracellular transport

• Project/Area Number: 16K08579
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kanazawa University
• Principal Investigator: Yoshioka Katsuji 金沢大学, がん進展制御研究所, 教授 (60200937)
• Research Collaborator: Gunarta I Ketut
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 細胞死 / 染色体 / マウス / 細胞分裂 / 足場タンパク質 / 遺伝子 / 神経科学 / 癌

Outline of Final Research Achievements

JSAP is known to function as an adaptor protein linking cargoes to kinesin/dynein motor proteins. We found that activated axonal JNK moves retrogradely in a dynein-dependent manner in JSAP-deficient neurons, and induces neuronal death. We also suggest that JSAP plays an important role in the regulation of intracellular transport system, and that its impairment by increased expression of JSAP or JSAP loss-of-function is likely to be causative for chromosome segregation errors in dividing cells.

Academic Significance and Societal Importance of the Research Achievements

本研究により、軸索輸送の破綻がもたらす神経細胞死は、多くの神経変性疾患に共通の現象である可能性が示唆された。神経細胞死の鍵となる分子を同定し、それらを標的にすることによって、多くの神経変性疾患に有効な治療薬の開発につなげることができると期待される。また、細胞分裂における染色体の不安定性は、がんをはじめとする疾病と密接に関連している。本研究成果は、正確な染色体分配を保証する普遍的な分子メカニズムの解明に貢献すると考えられる。

Research Products

• [Int'l Joint Research] モンゴル科学アカデミー総合実験生物学研究所(モンゴル)
• [Int'l Joint Research] モンゴル科学アカデミー総合実験生物学研究所(モンゴル)
• [Journal Article] JLP-JNK signaling protects cancer cells from reactive oxygen species-induced cell death (2018)
  • Author(s): Li Rong、Gunarta I. Ketut、Suzuki Ryusuke、Boldbaatar Jambaldorj、Nakazato Ryota、Yuliana Dewi、Davaakhuu Gantulga、Oyunsuren Tsendsuren、Takamatsu Nobuhiko、Kobayashi Masahiko、Hirao Atsushi、Yoshioka Katsuji
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 501 Issue: 3 Pages: 724-730
  • DOI: 10.1016/j.bbrc.2018.05.055
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] NF-κB activation is an early event of changes in gene regulation for acquiring drug resistance in human adenocarcinoma PC-9 cells (2018)
  • Author(s): Masashi Fukuoka, Katsuji Yoshioka, Hirohiko Hohjoh
  • Journal Title: PLoS One Volume: 13 Issue: 8 Pages: e0201796-e0201796
  • DOI: 10.1371/journal.pone.0201796
  • Peer Reviewed / Open Access
• [Journal Article] The osteopontin-CD44 axis in hepatic cancer stem cells regulates IFN signaling and HCV replication. (2018)
  • Author(s): Shirasaki T, Honda M, Yamashita T, Nio K, Shimakami T, Shimizu R, Nakasyo S, Murai K, Shirasaki N, Okada H, Sakai Y, Sato T, Suzuki T, Yoshioka K, Kaneko S.
  • Journal Title: Sci Rep. Volume: 8 Issue: 1 Pages: 13143-13143
  • DOI: 10.1038/s41598-018-31421-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Critical role of glioma-associated oncogene homolog 1 in maintaining invasive and mesenchymal-like properties of melanoma cells (2017)
  • Author(s): Gunarta I Ketut、Li Rong、Nakazato Ryota、Suzuki Ryusuke、Boldbaatar Jambaldorj、Suzuki Takeshi、Yoshioka Katsuji
  • Journal Title: Cancer Science Volume: 108 Issue: 8 Pages: 1602-1611
  • DOI: 10.1111/cas.13294
  • NAID: 120006336023
  • Peer Reviewed / Open Access
• [Journal Article] Scaffold protein JLP mediates TCR-initiated CD4 + T cell activation and CD154 expression (2017)
  • Author(s): Yan Qi、Yang Cheng、Fu Qiang、Chen Zhaowei、Liu Shan、Fu Dou、Rahman Rahmat N.、Nakazato Ryota、Yoshioka Katsuji、Kung Sam K.P.、Ding Guohua、Wang Huiming
  • Journal Title: Molecular Immunology Volume: 87 Pages: 258-266
  • DOI: 10.1016/j.molimm.2017.05.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Commentary: Critical role of JSAP1 and JLP in axonal transport in the cerebellar Purkinje cells of mice (2016)
  • Author(s): Katsuji Yoshioka
  • Journal Title: Journal of Neurology & Neuromedicine Volume: 1(8) Pages: 19-21
  • Peer Reviewed / Open Access
• [Presentation] Functional role of JSAP in mitotic chromosome segregation (2018)
  • Author(s): Gunarta IK, Nakazato R, Erdenebaatar P, Boldbaatar J, Suzuki R, Yoshioka K
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] Protective role of JLP-JNK pathway against oxidative stress-induced cell death (2018)
  • Author(s): Gunarta IK, Yoshioka K
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] Critical role of JSAP in axonal transport to prevent neuronal degeneration (2017)
  • Author(s): Yoshioka Katsuji、Sato Tokiharu
  • Organizer: 第60回日本神経化学会大会
  • Invited
• [Presentation] Functional role of GLI1 in maintaining mesenchymal-like and invasive phenotype of melanoma cells (2017)
  • Author(s): Gunarta I Ketut、Yoshioka Katsuji
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] Role of JLP in oxidative stress-induced cell death (2017)
  • Author(s): Gunarta I Ketut、Li Rong、Yoshioka Katsuji
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] Functional analysis of JSAP in the regulation of chromosome segregation (2017)
  • Author(s): Nakazato Ryota、Boldbaatar Jambaldorj、Yuliana Dewi、Suzuki Ryusuke、Yoshioka Katsuji
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] Overexpression of JSAP induces chromosome segregation errors (2017)
  • Author(s): Boldbaatar Jambaldorj、Nakazato Ryota、Yoshioka Katsuji
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] Role of the Gli1 transcription factor in melanoma metastasis (2016)
  • Author(s): I Ketut Gunarta, Katsuji Yoshioka
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] Role of JSAP in cell division control and cancer (2016)
  • Author(s): Ryota Nakazato, Katsuji Yoshioka
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] Role of scaffold protein JSAP in cancer (2016)
  • Author(s): Katsuji Yoshioka
  • Organizer: The 3rd International Symposium on Viral Hepatitis
  • Place of Presentation: Chengdu, China
  • Year and Date: 2016-06-27
  • Int'l Joint Research
• [Remarks]
  • URL: http://ganken.cri.kanazawa-u.ac.jp/yoshiokaHP/index.html
• [Remarks] 金沢大学がん進展制御研究所・善岡研究室ホームページ
  • URL: http://ganken.cri.kanazawa-u.ac.jp/yoshiokaHP/index.html