2020 Fiscal Year Research-status Report
Role of kinesin/dynein adaptor JSAP in reactive oxygen species-induced cell death and lysosome positioning
| Project/Area Number |
19K16737
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| Research Institution | Kanazawa University |
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Principal Investigator |
I・KETUT GUNARTA 金沢大学, がん進展制御研究所, 助教 (90838393)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | JSAP / JLP / JSAP1 / Curcumin / Autophagy / Lysosome |
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| Outline of Annual Research Achievements |
In the preset study I investigate the relationship between JSAP-mediated lysosome trafficking and cell death under acute oxidative stress condition. For the FY 2019, we established the role of JLP (JSAP2) in curcumin-induced cell death and clarified the molecular mechanisms. In FY 2020, we expanded our observation to JSAP1, a MAPK scaffold protein which has a similar structure to JLP (JSAP2). Unexpectedly, we found that JSAP1 and JLP differentially regulate curcumin/ROS-induced cell death. We also found that JSAP1 might have different role in autophagy proses to JLP, although further analysis is required. All of our observations have been published in peer-reviewed journal, two in 2020 and one in 2021.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
We have established shRNA-mediated knockdown and Crispr/Cas9-mediated knockout of JSAP1 in HCT116 (human colorectal cancer cell line). The results indicated that JSAP1 and JLP, despite a high sequence homology, are differently regulate curcumin-induced cell death. Analysis on autophagic flux unexpectedly showed an accumulation of autolysosome, suggesting that JSAP1 regulates autophagy at much later step, unlike previously expected. In addition, we expand our observation using normal human cell line (RPE1-hTERT), by knockdown of JLP using siRNA. Unexpectedly, unlike observation in cancer cell line, we observed a decreased in cell proliferation, suggesting a link between JSAP-mediated transport and cell proliferation.
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| Strategy for Future Research Activity |
For future analysis, we plan to analyze how JSAP-mediated transport may related to the cell proliferation of normal cells. We plan to analyze on different normal cell (e.g. primary mouse embryonic fibroblast) to see the generality of the phenotype. To get insight to the molecular mechanism, we plan to analyze the possibility of cell cycle arrest at a specific phase by FACS, and then analyze the expression of key genes at that particular phase.
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Research Products
(5 results)
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[Journal Article] c-Jun NH 2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) attenuates curcumin-induced cell death differently from its family member, JNK-associated leucine zipper protein (JLP)2021
Author(s)
I Ketut Gunarta, Dewi Yuliana, Purev Erdenebaatar, Yuhei Kishi, Jambaldorj Boldbaatar, Ryusuke Suzuki, Ravdandorj Odongoo, Gantulga Davaakhuu, Hirohiko Hohjoh, Katsuji Yoshioka
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Journal Title
Drug Discoveries & Therapeutics
Volume: 1
Pages: 21
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Peptidylarginine Deiminase 4 Promotes the Renal Infiltration of Neutrophils and Exacerbates the TLR7 Agonist-Induced Lupus Mice2020
Author(s)
Norio Hanata, Hirofumi Shoda, Hiroaki Hatano, Yasuo Nagafuchi, Toshihiko Komai, Tomohisa Okamura, Akari Suzuki, I Ketut Gunarta, Katsuji Yoshioka, Kazuhiko Yamamoto, Keishi Fujio
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Journal Title
Frontiers in immunology
Volume: 11
Pages: 1095
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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