研究実績の概要 |
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.
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