Eukaryotic Initiation Factor 6 (eIF6) controls translation by regulating 80S subunit formation. eIF6 is overexpressed in tumors. Here, we demonstrate that eIF6 inactivation delays tumorigenesis and reduces tumor growth in vivo. eIF6+/- mice resist to Myc-induced lymphomagenesis and have prolonged tumor-free survival and reduced tumor growth. eIF6+/- mice are also protected by p53 loss. Myc-driven lymphomas contain PKCβII and phosphorylated eIF6; eIF6 is phosphorylated by tumor-derived PKCβII, but not by the eIF4F activator mTORC1. Mutation of PKCβII phosphosite of eIF6 reduces tumor growth. Thus, eIF6 is a rate-limiting controller of initiation of translation, able to affect tumorigenesis and tumor growth. Modulation of eIF6 activity, independent from eIF4F complex, may lead to a therapeutical avenue in tumor therapy.
|Titolo:||Impairment of cytoplasmic eIF6 activity restricts lymphomagenesis and tumor progression without affecting normal growth|
BIFFO, STEFANO (Corresponding)
|Parole Chiave:||protein-kinase-C; B-cell lymphoma; translation initiation; binding protein; leukemia-cells; cancer; ribosome; P27(BBP); MYC; RACK1|
|Settore Scientifico Disciplinare:||Settore BIO/06 - Anatomia Comparata e Citologia|
|Data di pubblicazione:||14-giu-2011|
|Digital Object Identifier (DOI):||10.1016/j.ccr.2011.04.018|
|Appare nelle tipologie:||01 - Articolo su periodico|