MNK1-induced eIF-4E phosphorylation in myeloma cells: a pathway mediating IL-6-induced expansion and expression of genes involved in metabolic and proteotoxic responses.

ABSTRACT: Because multiple myeloma (MM) cells are at risk for endoplasmic reticulum (ER) stress, they require a carefully regulated mechanism to promote protein translation of selected transcripts when proliferation is stimulated. MAPK-interacting kinases (MNKs) may provide this mechanism by enhancing cap-dependent translation of a small number of critical transcripts. We, thus, tested whether MNKs played a role in MM responses to the myeloma growth factor interleukin-6 (IL-6). IL-6 activated MNK1 phosphorylation and induced phosphorylation of its substrate, eIF-4E, in MM lines and primary specimens. MNK paralysis, achieved pharmacologically or by shRNA, prevented MM expansion stimulated by IL-6. A phosphodefective eIF-4E mutant also prevented the IL-6 response, supporting the notion that MNK's role

SUBMITTER: Shi Y 

PROVIDER: S-EPMC3979714 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature