MNKs act as a regulatory switch for eIF4E1 and eIF4E3 driven mRNA translation in DLBCL.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25403230.
- Also identified by DOI 10.1038/ncomms6413 and PMC identifier 4238046.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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) and show a distinct distribution of MNK1 and MNK2 in germinal centre B-cell (GCB) and activated B-cell (ABC) DLBCL. Despite displaying a differential distribution in GCB and ABC, both MNKs functionally complement each other to sustain cell survival. MNK inhibition ablates eIF4E1 phosphorylation and concurrently enhances eIF4E3 expression. Loss of MNK protein itself downregulates total eIF4E1 protein level by reducing eIF4E1 mRNA polysomal loading without affecting total mRNA level or stability. Enhanced eIF4E3 expression marginally suppresses eIF4E1-driven translation but exhibits a unique translatome that unveils a novel role for eIF4E3 in translation initiation. We propose that MNKs can modulate oncogenic translation by regulating eIF4E1-eIF4E3 levels and activity in DLBCL.
Medical subject headings
- Eukaryotic Initiation Factor-4E
- Intracellular Signaling Peptides and Proteins
- Lymphoma, Large B-Cell, Diffuse
- Protein Biosynthesis
- Protein Serine-Threonine Kinases
- RNA, Messenger