PMID- 29753743 OWN - NLM STAT- MEDLINE DCOM- 20190513 LR - 20190513 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 501 IP - 3 DP - 2018 Jun 27 TI - JLP-JNK signaling protects cancer cells from reactive oxygen species-induced cell death. PG - 724-730 LID - S0006-291X(18)31104-5 [pii] LID - 10.1016/j.bbrc.2018.05.055 [doi] AB - Oxidative stress, which can be caused by an overproduction of reactive oxygen species (ROS), often leads to cell death. In recent years, c-Jun NH(2)-terminal kinase (JNK)-associated leucine zipper protein (JLP, also known as SPAG9 or JIP4), a scaffold protein for JNK mitogen-activated protein kinase (MAPK) signaling pathways, was found to serve as a novel biomarker for cancer. However, although JNK MAPK pathways are reported to be activated in response to various stimuli, including oxidative stress, whether JLP is involved in ROS signaling remains unknown. In this study, we examined the role of JLP in hydrogen peroxide (H(2)O(2))-induced cancer cell death, and found that JLP knockdown (KD) cells exhibit a substantially enhanced cell death response, along with increased intracellular ROS levels. This is the first demonstration of a protective role for JLP in response to cell-death stimulation. We also found that the H(2)O(2)-induced JNK activation was attenuated in JLP KD cancer cells. The decreases in cell viability and JNK activation in the JLP KD cells were almost completely reversed by expressing wild-type JLP, but not a mutant JLP lacking the JNK-binding domain. These data collectively suggest that the JLP-JNK signaling pathway counteracts ROS-induced cancer cell death. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Li, Rong AU - Li R AD - Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. FAU - Gunarta, I Ketut AU - Gunarta IK AD - Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. FAU - Suzuki, Ryusuke AU - Suzuki R AD - Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. FAU - Boldbaatar, Jambaldorj AU - Boldbaatar J AD - Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. FAU - Nakazato, Ryota AU - Nakazato R AD - Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. FAU - Yuliana, Dewi AU - Yuliana D AD - Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. FAU - Davaakhuu, Gantulga AU - Davaakhuu G AD - Laboratory of Molecular Biology, Institute of General and Experimental Biology, Mongolian Academy of Sciences, Ulaanbaatar, Mongolia. FAU - Oyunsuren, Tsendsuren AU - Oyunsuren T AD - Laboratory of Molecular Biology, Institute of General and Experimental Biology, Mongolian Academy of Sciences, Ulaanbaatar, Mongolia. FAU - Takamatsu, Nobuhiko AU - Takamatsu N AD - Laboratory of Molecular Biology, Department of Biosciences, School of Science, Kitasato University, Sagamihara, Japan. FAU - Kobayashi, Masahiko AU - Kobayashi M AD - Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. FAU - Hirao, Atsushi AU - Hirao A AD - Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kanazawa, Japan. FAU - Yoshioka, Katsuji AU - Yoshioka K AD - Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. Electronic address: katsuji@staff.kanazawa-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Reactive Oxygen Species) RN - 0 (SPAG9 protein, human) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - Adaptor Proteins, Signal Transducing/*metabolism MH - Cell Death MH - Cell Line, Tumor MH - Humans MH - Hydrogen Peroxide/metabolism MH - *MAP Kinase Signaling System MH - Neoplasms/*metabolism/pathology MH - *Oxidative Stress MH - Reactive Oxygen Species/*metabolism OTO - NOTNLM OT - Cell death OT - JNK OT - Oxidative stress OT - ROS OT - Scaffold protein EDAT- 2018/05/14 06:00 MHDA- 2019/05/14 06:00 CRDT- 2018/05/14 06:00 PHST- 2018/05/05 00:00 [received] PHST- 2018/05/09 00:00 [accepted] PHST- 2018/05/14 06:00 [pubmed] PHST- 2019/05/14 06:00 [medline] PHST- 2018/05/14 06:00 [entrez] AID - S0006-291X(18)31104-5 [pii] AID - 10.1016/j.bbrc.2018.05.055 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2018 Jun 27;501(3):724-730. doi: 10.1016/j.bbrc.2018.05.055.