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

Lipton JO, Yuan ED, Boyle LM, Ebrahimi-Fakhari D, Kwiatkowski E, Nathan A, Güttler T, Davis F, Asara JM, Sahin M · 2015 · Cell · Atlas ID LIP2015

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.

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At a glance

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	2026-09-23
Source	DOI 10.1016/j.cell.2015.04.002 · PMID 25981667 · Free full text (PMC4447213)

Extracted findings

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

In the Atlas

Cite this paper

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Lipton, J. O., Yuan, E. D., Boyle, L. M., Ebrahimi-Fakhari, D., Kwiatkowski, E., Nathan, A., Güttler, T., Davis, F., Asara, J. M., & Sahin, M. (2015). The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated Phosphorylation. Cell. https://doi.org/10.1016/j.cell.2015.04.002

@article{LIP2015,
  author       = {Lipton, J. O. and Yuan, E. D. and Boyle, L. M. and Ebrahimi-Fakhari, D. and Kwiatkowski, E. and Nathan, A. and Güttler, T. and Davis, F. and Asara, J. M. and Sahin, M.},
  title        = {{The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated Phosphorylation}},
  journal      = {Cell},
  year         = {2015},
  doi          = {10.1016/j.cell.2015.04.002},
  note         = {PMID: 25981667},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record LIP2015) [Data set]. https://mtor-atlas.org/study/LIP2015/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_LIP2015,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record LIP2015},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/LIP2015/},
  doi          = {10.5281/zenodo.22059963}
}