title: JNK2 is activated during ER stress and promotes cell survival.
abstract: Adaptation to endoplasmic reticulum (ER) stress relies on activation of the unfolded protein response (UPR) and induction of autophagy. Indeed, cells die if ER stress is not countered by the UPR. Here we show in U937 cells that the ER stressors tunicamycin and thapsigargin cause increased expression of c-Jun N-terminal kinase 2 (JNK2), which allows regulation of the UPR, whose silencing or pharmacological inhibition delays BiP (immunoglobulin heavy-chain binding protein) upregulation, and causes earlier and greater expression of CCAAT/enhancer-binding protein-homologous protein (CHOP). Furthermore, we show that pharmacological inhibition or silencing of JNK2 causes accumulation of both p62 and the acidic compartment, caspase 3 activation and apoptosis. Our results reveal that JNK2 prevents accumulation of the acidic compartment in U937 cells undergoing autophagic flux and, by this mechanism, it keeps stressed cells alive. Our findings highlight a potential role for JNK2 in tumor cell survival, senescence and neurodegenerative diseases, in which ER stress, autophagy and lysosome activity are known to interplay.
authors.affiliation: Department of Experimental Medicine, Viale Regina Elena 324, Sapienza University of Rome, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Raciti
authors.forename: L V
authors.initials: LV
authors.lastname: Lotti
authors.forename: S
authors.initials: S
authors.lastname: Valia
authors.forename: F M
authors.initials: FM
authors.lastname: Pulcinelli
authors.forename: L
authors.initials: L
authors.lastname: Di Renzo
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D020298:U937 Cells
chemical_list: C497249:DDIT3 protein, human; D016271:Proto-Oncogene Proteins c-myc; D051742:Transcription Factor CHOP; D048056:Mitogen-Activated Protein Kinase 9; D053148:Caspase 3