Translational Control of Metabolism Identifies New Intervention Targets for Cancer And Metabolic Disorders

Seminar CNR-CIBIO

17 February 2020
Versione stampabile

Location: Polo F. Ferrari 2, via Sommarive 9 (Povo) – Room B101
Time: 14.00

Speaker

  • Stefano Biffo - University of Milano & Program Leader INGM "Romeo ed Enrica Invernizzi",​ Milan, Italy

Abstract

Eukaryotic initiation factor 6 (eIF6) is necessary for the nucleolar biogenesis of 60S ribosomes.
However, most of eIF6 resides in the cytoplasm, where it acts as an initiation factor. eIF6 is necessary
for maximal protein synthesis downstream of growth factor stimulation. We show that mechanistically, eIF6 acts through the regulation of reinitiation at uORFs. Inhibition of eIF6 activity in mouse models has a dramatic impact on cancer malignancy and metabolic syndromes, driven by the specific translation of uORF-containing transcription factor mRNAs. Finally, inhibition of eIF6 activity by new drugs reverts the negative effects of the overexpression aand/or hyperphosphorylation of eIF6.