Aberrant Proteostasis of BMAL1 Underlies Circadian Abnormalities in a Paradigmatic mTOR-opathy

Lipton JO, Boyle LM, Yuan ED, Hochstrasser KJ, Chifamba FF, Nathan A, Tsai PT, Davis F, Sahin M · 2017 · Cell Reports · Atlas ID LIP2017

What this study shows

In mouse models of tuberous sclerosis, where mTOR is stuck on, the circadian clock ran abnormally: poor timekeeping in constant conditions and exaggerated responses to phase resetting. mTOR raised BMAL1 levels by changing its translation, degradation and location; genetically lowering BMAL1 rescued the behavioural rhythm defects. Constant, unpatterned mTOR activity disturbs a rhythm downstream.

Abstract

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Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder characterized by mutations in either the TSC1 or TSC2 genes, whose products form a critical inhibitor of the mechanistic target of rapamycin (mTOR). Loss of TSC1/2 gene function renders an mTOR-overactivated state. Clinically, TSC manifests with epilepsy, intellectual disability, autism, and sleep dysfunction. Here, we report that mouse models of TSC have abnormal circadian rhythms. We show that mTOR regulates the proteostasis of the core clock protein BMAL1, affecting its translation, degradation, and subcellular localization.

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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 models of tuberous sclerosis complex (Tsc1/Tsc2 loss)); 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 models of tuberous sclerosis complex (Tsc1/Tsc2 loss)
Journal	Cell Reports
Year	2017
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1016/j.celrep.2017.07.008 · PMID 28746872 · Free full text (PMC5603761)

Extracted findings

Intervention	Genetic loss of Tsc1/Tsc2; reduced Bmal1 dose
Target	mTOR; BMAL1 proteostasis
Model	Mouse
Effect	mTOR overactivation elevates BMAL1 and disrupts circadian timekeeping; lowering BMAL1 rescues behaviour

In the Atlas

Cite this paper

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Lipton, J. O., Boyle, L. M., Yuan, E. D., Hochstrasser, K. J., Chifamba, F. F., Nathan, A., Tsai, P. T., Davis, F., & Sahin, M. (2017). Aberrant Proteostasis of BMAL1 Underlies Circadian Abnormalities in a Paradigmatic mTOR-opathy. Cell Reports. https://doi.org/10.1016/j.celrep.2017.07.008

@article{LIP2017,
  author       = {Lipton, J. O. and Boyle, L. M. and Yuan, E. D. and Hochstrasser, K. J. and Chifamba, F. F. and Nathan, A. and Tsai, P. T. and Davis, F. and Sahin, M.},
  title        = {{Aberrant Proteostasis of BMAL1 Underlies Circadian Abnormalities in a Paradigmatic mTOR-opathy}},
  journal      = {Cell Reports},
  year         = {2017},
  doi          = {10.1016/j.celrep.2017.07.008},
  note         = {PMID: 28746872},
}

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 LIP2017) [Data set]. https://mtor-atlas.org/study/LIP2017/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_LIP2017,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record LIP2017},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/LIP2017/},
  doi          = {10.5281/zenodo.22059963}
}