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“The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated Phosphorylation”

June 1, 2015

The 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. HMS researchers, led by Jonathan Lipton and Mustafa Sahin, show that the key circadian transcription factor BMAL1 associates with the translational machinery in the cytosol and promotes protein synthesis (to read summary and access article, click here). 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. 

Jonathan O. Lipton, Elizabeth D. Yuan, Lara M. Boyle, Darius Ebrahimi-Fakhari, Erica Kwiatkowski, Ashwin Nathan, Thomas G├╝ttler, Fred Davis, John M. Asara, Mustafa Sahin

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