Dataset Information


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

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 down-regulates 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. Together, we propose that MNKs can modulate oncogenic translation by regulating eIF4E1-eIF4E3 levels and activity in DLBCL. As the knockdown of eIF4E1 or eIF4E3 caused significant cell death, we overexpressed either protein in HLY-1 cells and performed sucrose density gradient fractionation. RNA was extracted from polysome fractions #9-10, containing highly translated polysome-bound mRNAs, from total RNA and from an empty vector control. These samples, in triplicate, were used for either translatome or transcriptome analysis using Illumina HumanHT-12 v4 BeadChips for gene expression analysis.

ORGANISM(S): Homo sapiens  

SUBMITTER: Anup Mahurkar  Kevin G Becker   Laurent Volpone   Amol C Shetty   Simone Houng   Elin Lehrmann   Krystyna Mazan-Mamczarz   Yongqing Zhang   Parameswary A Muniandy   Raymond Peroutka   James Steinhardt   Katherine L Borden   Ronald B Gartenhaus   Ari L Landon   Bojie Daia    

PROVIDER: E-GEOD-61691 | ArrayExpress | 2014-11-28



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