title: ATF4 activation by the p38MAPK-eIF4E axis mediates apoptosis and autophagy induced by selenite in Jurkat cells.
abstract: Previous studies have shown that selenite exerts pro-apoptosis and pro-autophagy effects and is associated with the activation of ER stress in T-cell acute lymphoblastic leukemia (T-ALL). Herein we demonstrate the underlying mechanisms by which the activation of p38MAPK plays essential roles in apoptosis and autophagy and the coordination of cellular metabolic processes during leukemia therapy. MKK3/6-dependent activation of p38MAPK is required for the phosphorylation of eIF4E, thus initiating the translation of ER stress-related transcription factor ATF4. Upregulated ATF4 results in the transcriptional initiation of the apoptosis-related chop gene and autophagy-related map1lc3b gene, through which selenite links ER stress to apoptosis and autophagy during leukemia treatment. Moreover, autophagy induction enhances cell apoptosis under this condition.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medicine Sciences & School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Kejian
authors.initials: K
authors.lastname: Shi
authors.forename: Pa
authors.initials: P
authors.lastname: Wu
authors.forename: Jiajia
authors.initials: J
authors.lastname: An
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Caimin
authors.initials: C
authors.lastname: Xu
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D004721:Endoplasmic Reticulum / Q000187:drug effects; D004789:Enzyme Activation; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D060888:Real-Time Polymerase Chain Reaction; D018038:Sodium Selenite / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C497109:ATF4 protein, human; D039561:Eukaryotic Initiation Factor-4E; D051701:Activating Transcription Factor 4; D048051:p38 Mitogen-Activated Protein Kinases; D018038:Sodium Selenite
keywords: 17-AAG; 17-allylamino-demethoxygeldamycin; ATF4; Apoptosis; Autophagy; Hsp90; Sodium selenite; eIF2α; eIF4E; eukaryotic translation initiation factor 2 subunit alpha; eukaryotic translation initiation factor 4E; heat shock protein 90; p38MAPK; s.c.; subcutaneous injection