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Curcumin, a major component of turmeric, is known to exhibit multiple biological functions including antitumor activity. We previously reported that the mitogen-activated protein kinase (MAPK) scaffold protein c-Jun NH2-terminal kinase (JNK)-associated leucine zipper protein (JLP) reduces curcumin-induced cell death by modulating p38 MAPK and autophagy through the regulation of lysosome positioning. In this study, we investigated the role of JNK/stress-activated protein kinase-associated protein 1 (JSAP1), a JLP family member, in curcumin-induced stress, and found that JSAP1 also attenuates curcumin-induced cell death. However, JSAP1 knockout showed no or little effect on the activation of JNK and p38 MAPKs in response to curcumin. In addition, small molecule inhibitors of JNK and p38 MAPKs did not increase curcumin-induced cell death. Furthermore, JSAP1 depletion did not impair lysosome positioning and autophagosome-lysosome fusion. Instead, we noticed substantial autolysosome accumulation accompanied by an inefficient autophagic flux in JSAP1 knockout cells. Taken together, these results indicate that JSAP1 is involved in curcumin-induced cell death differently from JLP, and may suggest that JSAP1 plays a role in autophagosome degradation and its dysfunction results in enhanced cell death. The findings of this study may contribute to the development of novel therapeutic approaches using curcumin for cancer.

Lysosomes are involved in many cellular functions, and in turn lysosomal dysfunction underlies a variety of diseases, including cancer and neurodegenerative diseases. Lysosomes are distributed broadly in the cytoplasm and can move throughout the cell in kinesin- and dynein-dependent manners. Although many mechanisms of lysosomal transport have been reported, how lysosomal transport is regulated has yet to be fully elucidated. In this study we analyzed c-Jun NH2-terminal kinase-associated leucine zipper protein (JLP), an adaptor of kinesin and dynein motor proteins, and found that lysosomes were localized toward the cell periphery in JLP knockdown cells, leading to the impairment of autophagosome-lysosome fusion. Furthermore, we performed rescue experiments using wild-type JLP and its various deletion mutants. The results indicated that JLP may regulate lysosome localization and autophagy through interaction of JLP with kinesin-1 heavy chain, but not with dynactin p150Glued or lysosomal transmembrane protein 55b. Our findings provide new insights into the mechanisms of lysosomal trafficking regulation. This study contributes to the understanding of how lysosomes exert their multiple functions, potentially leading to the identification of molecular targets for diseases caused by lysosomal dysfunction.

Curcumin, a major component of turmeric, is known to exhibit multiple biological functions including antitumor activity. We previously reported that the mitogen-activated protein kinase (MAPK) scaffold protein c-Jun NH

Lysosomes are involved in many cellular functions, and in turn lysosomal dysfunction underlies a variety of diseases, including cancer and neurodegenerative diseases. Lysosomes are distributed broadly in the cytoplasm and can move throughout the cell in kinesin- and dynein-dependent manners. Although many mechanisms of lysosomal transport have been reported, how lysosomal transport is regulated has yet to be fully elucidated. In this study we analyzed c-Jun NH