The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated Phosphorylation
| Autor: | Mustafa Sahin, Lara M. Boyle, John M. Asara, Darius Ebrahimi-Fakhari, Jonathan O. Lipton, Erica Kwiatkowski, Ashwin Nathan, Elizabeth D. Yuan, Fred C. Davis, Thomas Güttler |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
endocrine system
ARNTL Transcription Factors Biochemistry Genetics and Molecular Biology(all) Circadian clock P70-S6 Kinase 1 Biology Ribosomal Protein S6 Kinases 90-kDa Article General Biochemistry Genetics and Molecular Biology Cell biology Circadian Clocks Animals Casein kinase 1 Circadian rhythm Translation factor Protein kinase A Transcription factor |
| Zdroj: | Cell. 161(5):1138-1151 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2015.04.002 |
| Popis: | SummaryThe circadian timing system synchronizes cellular function by coordinating rhythmic transcription via a transcription-translational feedback loop. How the circadian system regulates gene expression at the translational level remains a mystery. Here, we show that the key circadian transcription factor BMAL1 associates with the translational machinery in the cytosol and promotes protein synthesis. The mTOR-effector kinase, ribosomal S6 protein kinase 1 (S6K1), an important regulator of translation, rhythmically phosphorylates BMAL1 at an evolutionarily conserved site. S6K1-mediated phosphorylation is critical for BMAL1 to both associate with the translational machinery and stimulate protein synthesis. Protein synthesis rates demonstrate circadian oscillations dependent on BMAL1. Thus, in addition to its critical role in circadian transcription, BMAL1 is a translation factor that links circadian timing and the mTOR signaling pathway. More broadly, these results expand the role of the circadian clock to the regulation of protein synthesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|