The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated Phosphorylation
What this study shows
S6K1, a main output of mTORC1, phosphorylates the clock protein BMAL1 rhythmically, and that phosphorylation lets BMAL1 join the translation machinery and drive protein synthesis. Protein synthesis rates oscillated over the day in a BMAL1-dependent way. A direct molecular bridge between mTORC1 output and the 24-hour clock.
Abstract
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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. 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.
Read the full abstract on PubMed →At a glance
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| Evidence type | A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse tissues and cultured cells); the code names the system studied -- animal work can be rigorous and still not be human data. |
| Study type | 4 - Animal Study |
| Model system | Mouse tissues and cultured cells |
| Journal | Cell |
| Year | 2015 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1016/j.cell.2015.04.002 · PMID 25981667 · Free full text (PMC4447213) |
Where this study fits
How this study connects to the pathway map, open questions, people and other studies in the Atlas.
People in the Atlas
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First author of the two studies that tie mTOR signalling to the circadian clock protein BMAL1: S6K1 phosphorylates BMAL1 to drive translation, and constant mTOR activity in tuberous sclerosis disturbs the clock.
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Senior author of the studies showing that mTOR signalling reaches the circadian clock through BMAL1, and a physician-scientist focused on tuberous sclerosis, the classic disease of overactive mTOR.
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Second author on the study showing that S6K1 phosphorylates BMAL1 to link mTOR signalling with circadian protein synthesis, and co-author on the follow-up in tuberous sclerosis models.
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Research assistant at Boston Children's Hospital who co-authored both studies linking mTOR to the clock protein BMAL1, including the tuberous sclerosis study where she was second author.
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Co-author on both Boston Children's Hospital studies linking mTOR signalling to the circadian clock protein BMAL1.
More: 5 other authors
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Circadian biologist from Northeastern University who brought expertise on the brain's master clock to two studies linking mTOR and the clock protein BMAL1.
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Mass-spectrometry specialist whose core facility supplied metabolomics and proteomics for several mTOR studies, including measurements of purine, pyrimidine and SAM metabolism downstream of mTORC1.
No profile yet: Ebrahimi-Fakhari D, Kwiatkowski E, Güttler T
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Topics
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | Genetic and biochemical manipulation of BMAL1 phosphorylation |
| Target | S6K1; BMAL1; translation |
| Model | Mouse |
| Effect | S6K1 rhythmically phosphorylates BMAL1; protein synthesis shows BMAL1-dependent circadian oscillation |
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