Role of kinesin/dynein adaptor JSAP in reactive oxygen species-induced cell death and lysosome positioning

2021 Fiscal Year Annual Research Report

• Project/Area Number: 19K16737
• Research Institution: Kanazawa University
• Principal Investigator: I・KETUT GUNARTA 金沢大学, がん進展制御研究所, 助教 (90838393)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: JSAP / JLP / JSAP1 / Curcumin / Autophagy / Lysosome

Outline of Annual Research Achievements

Cell executes autophagy as a survival system under oxidative stress and the process of autophagy is tightly linked to the activity and the
position of the lysosome. Curcumin is a natural compound that exhibits anticancer properties. Autophagy is one survival mechanism under curcumin-induced stress. In this study, I investigated the role of JSAP in autophagy and the survival of cancer cells under curcumin treatment. Throughout this study, we have clarified several key functions of JSAP in curcumin-induced stress. (1) We have clarified that JSAP1 and JSAP2 (a.k.a. JLP) differently protect cells from curcumin-induced cell death. (2) Protective role of JSAP2 is related to its function as a scaffold protein of p38 MAPK and retrograde transport of lysosomes. (3) The kinesin-1 heavy chain binding domain (KBD) but not dynactin p150Glued
binding domain (DBD) of JLP is required for the regulation of lysosome trafficking and autophagy. (4) Unlike JSAP2, JSAP1 exerts its protective role independent of its function as a MAPK scaffold protein. JSAP1 also does not involve in retrograde transport of lysosomes but may involve in autophagosome degradation. Overall, our study clarified the role of JSAP in curcumin-induced stress and highlighted autophagy as a survival mechanism.

Research Products

• [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
  • Journal Title: Drug Discoveries & Therapeutics Volume: 1 Pages: 21
  • DOI: 10.5582/ddt.2021.01021
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Role of JSAP2 in cell cycle regulation (2021)
  • Author(s): I Ketut Gunarta
  • Organizer: the 44th annual meeting of the molecular biology society of Japan
  • Int'l Joint Research