Abstract
Eukaryotic translation initiation factor 6 (eIF6) is essential for the synthesis of 60S ribosomal subunits and for regulating the association of 60S and 40S subunits. A mechanistic understanding of how eIF6 modulates translation in response to stress, specifically starvation-induced stress, is lacking. We here show a novel mode of eIF6 regulation by glycogen synthase kinase 3 (GSK3) that is predominantly active in response to serum starvation. Both GSK3α and GSK3β phosphorylate human eIF6. Multiple residues in the C terminus of eIF6 are phosphorylated by GSK3 in a sequential manner. In response to serum starvation, eIF6 accumulates in the cytoplasm, and this altered localization depends on phosphorylation by GSK3. Disruption of eIF6 phosphorylation exacerbates the translation inhibitory response to serum starvation and stalls cell growth. These results suggest that eIF6 regulation by GSK3 contributes to the attenuation of global protein synthesis that is critical for adaptation to starvation-induced stress.
Highlights
Eukaryotic initiation factor 6 is a key modulator of translation initiation that regulates the biogenesis and availability of the 60S ribosomal subunits [1,2,3]. eIF6 directly associates with pre-60S complexes in the nucleolus and is exported into the cytoplasm in complex with the 60S where it aids in 60S maturation [4,5,6,7,8]
Here we report a novel regulation of eIF6 by glycogen synthase kinase 3 (GSK3) that is active under conditions of serum starvation-induced stress
We show that the regulation of translation initiation factor eIF6 by GSK3 affects translation response to starvation
Summary
Eukaryotic initiation factor 6 (eIF6) is a key modulator of translation initiation that regulates the biogenesis and availability of the 60S ribosomal subunits [1,2,3]. eIF6 directly associates with pre-60S complexes in the nucleolus and is exported into the cytoplasm in complex with the 60S where it aids in 60S maturation [4,5,6,7,8]. Because GSK3 is activated under serum-starved conditions, we determined whether eIF6 is phosphorylated in serumstarved 293T cells by MS. This was confirmed by probing for eIF6 protein levels in response to longterm serum starvation when GSK3 is fully active.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
