MNKs act as a regulatory switch for eIF4E1 and eIF4E3 driven mRNA translation in DLBCL

• DOI: 10.1038/ncomms6413
• Publication Date: 2014-11-18T13:20:01Z
• Authors: Ari L. Landon; Parameswary A. Mu...; Amol C. Shetty; Elin Lehrmann; Laurent Volpon; Simone Houng; Yongqing Zhang; Bojie Dai; Raymond Peroutka; Krystyna Mazan-Ma...; James Steinhardt; Anup Mahurkar; Kevin G. Becker; Katherine L. Borden; Ronald B. Gartenhaus
• Keywords: EIF4E; Eukaryotic translation; Translational regulation

Abstract The phosphorylation of eIF4E1 at serine 209 by MNK1 or MNK2 has been shown to initiate oncogenic mRNA translation, a process that favours cancer development and maintenance. Here, we interrogate the MNK-eIF4E axis in diffuse large B-cell lymphoma (DLBCL) show distinct distribution germinal centre (GCB) activated (ABC) DLBCL. Despite displaying differential GCB ABC, both MNKs functionally complement each other sustain cell survival. MNK inhibition ablates concurrently enhances eIF4E3 expression. Loss protein itself downregulates total level reducing polysomal loading without affecting stability. Enhanced expression marginally suppresses eIF4E1-driven translation but exhibits unique translatome unveils novel role for initiation. We propose can modulate regulating eIF4E1-eIF4E3 levels activity