Phosphorylation of eIF-4E positively regulates formation of the eIF-4F translation initiation complex following DNA damage.
The eukaryotic translation initiation factor 4E (eIF-4E) is essential for cap-dependent protein translation. However, the role of eIF-4E phosphorylation in protein translation is still unclear. In this study, the function of eIF-4E phosphorylation in the formation of the translational initiation complex eIF-4F following DNA damage was investigated. Our results show that etoposide treatment caused a rapid increase in eIF-4E phosphorylation. The addition of CGP57380, a specific inhibitor of the eIF-4E kinase Mnk, not only inhibited eIF-4E phosphorylation but also resulted in reduced interaction between eIF-4E and eIF-4G. Furthermore, neither the p38 MAPK inhibitor nor the ERK inhibitor caused significant inhibition in eIF-4E phosphorylation induced by etoposide. However, a JNK-specific inhibitor, SP600125, strongly suppressed etoposide-induced eIF-4E phosphorylation. Our results provide the first evidence indicating that phosphorylation of eIF-4E by Mnk, possibly mediated by JNK or JNK-like kinases, is critical for formation of the translational initiation complex eIF-4F following DNA damage.
Zhang
Ying
Y
The Division of Basic Biomedical Sciences, University of South Dakota, Sanford School of Medicine, 414 E. Clark Street, Lee Medical Building, Vermillion, SD 57069, USA.
Li
Yan
Y
Yang
Da-Qing
DQ
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology*; D039562:Eukaryotic Initiation Factor-4F / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects* / Q000502:physiology; D010448:Peptide Initiation Factors / Q000378:metabolism; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D039562:Eukaryotic Initiation Factor-4F; D010448:Peptide Initiation Factors; D005047:Etoposide; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases