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: Qian Jiang, Feng Li, Kejian Shi, Pa Wu, Jiajia An, Yang Yang, Caimin Xu
• Journal: FEBS letters (FEBS Lett) Vol. 587 Issue 15 Pg. 2420-9 (Aug 02 2013) ISSN: 1873-3468 [Electronic] England
• PMID: 23792164 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Chemical References

• ATF4 protein, human
• Eukaryotic Initiation Factor-4E
• Activating Transcription Factor 4
• p38 Mitogen-Activated Protein Kinases
• Sodium Selenite

Topics

• Activating Transcription Factor 4 (metabolism)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Endoplasmic Reticulum (drug effects)
• Enzyme Activation
• Eukaryotic Initiation Factor-4E (metabolism)
• Humans
• Jurkat Cells
• Real-Time Polymerase Chain Reaction
• Sodium Selenite (pharmacology)
• p38 Mitogen-Activated Protein Kinases (metabolism)