| First Author | Zidek LM | Year | 2015 |
| Journal | EMBO Rep | Volume | 16 |
| Issue | 8 | Pages | 1022-36 |
| PubMed ID | 26113365 | Mgi Jnum | J:224539 |
| Mgi Id | MGI:5688233 | Doi | 10.15252/embr.201439837 |
| Citation | Zidek LM, et al. (2015) Deficiency in mTORC1-controlled C/EBPbeta-mRNA translation improves metabolic health in mice. EMBO Rep 16(8):1022-36 |
| abstractText | The mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of physiological adaptations in response to changes in nutrient supply. Major downstream targets of mTORC1 signalling are the mRNA translation regulators p70 ribosomal protein S6 kinase 1 (S6K1p70) and the 4E-binding proteins (4E-BPs). However, little is known about vertebrate mRNAs that are specifically controlled by mTORC1 signalling and are engaged in regulating mTORC1-associated physiology. Here, we show that translation of the CCAAT/enhancer binding protein beta (C/EBPbeta) mRNA into the C/EBPbeta-LIP isoform is suppressed in response to mTORC1 inhibition either through pharmacological treatment or through calorie restriction. Our data indicate that the function of 4E-BPs is required for suppression of LIP. Intriguingly, mice lacking the cis-regulatory upstream open reading frame (uORF) in the C/EBPbeta-mRNA, which is required for mTORC1-stimulated translation into C/EBPbeta-LIP, display an improved metabolic phenotype with features also found under calorie restriction. Thus, our data suggest that translational adjustment of C/EBPbeta-isoform expression is one of the key processes that direct metabolic adaptation in response to changes in mTORC1 activity. |
