Oliver's mTOR Atlas Evidence Platform
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Phosphorylation of OTUB1 promotes autophagy initiation under starvation

Sun L, Lian J et al. · 2026 · Nature Communications · Atlas ID SUN2026B

What this study shows

Under starvation, ERK phosphorylates the deubiquitinase OTUB1 at S118, which stabilizes it by letting it out-compete TRIM29 for binding to ANXA2. Stabilized OTUB1 upregulates DEPTOR, a natural mTOR inhibitor, which suppresses mTOR and triggers autophagy. In mice, restoring this fasting-triggered ERK-OTUB1-DEPTOR-mTOR axis countered the mTOR-activating effect of a Western diet and eased MASLD (fatty liver disease) progression, giving a mechanistic account of how fasting benefits the liver.

Abstract

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Eukaryotes initiate autophagy in response to environmental challenges such as nutrient deprivation. However, the mechanisms governing autophagy initiation remain incompletely understood. Here, we demonstrated that OTUB1 phosphorylation plays a key role in starvation-induced autophagy initiation. Specifically, ERK phosphorylates OTUB1 at S118 during starvation. This phosphorylation enables competitive binding of ANXA2 to OTUB1, disrupting its interaction with TRIM29 and enhancing OTUB1 stability. Stabilized OTUB1 upregulated DEPTOR, thereby inhibiting mTOR and inducing autophagy.

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At a glance

Evidence type M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Mouse (Western diet / MASLD model); cultured cells (starvation)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type5 - Mechanistic / In Vitro
Model systemMouse (Western diet / MASLD model); cultured cells (starvation)
JournalNature Communications
Year2026
Peer reviewedYes
Record last updated2026-09-23
SourceDOI 10.1038/s41467-026-76796-7 · PMID 42736303 · Free full text (PMC13574767)

Cite this paper

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Sun, L., et al. (2026). Phosphorylation of OTUB1 promotes autophagy initiation under starvation. Nature Communications. https://doi.org/10.1038/s41467-026-76796-7

@article{SUN2026B,
  author       = {Sun, L. and Lian, J. and others},
  title        = {{Phosphorylation of OTUB1 promotes autophagy initiation under starvation}},
  journal      = {Nature Communications},
  year         = {2026},
  doi          = {10.1038/s41467-026-76796-7},
  note         = {PMID: 42736303},
}

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 SUN2026B) [Data set]. https://mtor-atlas.org/study/SUN2026B/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SUN2026B,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SUN2026B},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SUN2026B/},
  doi          = {10.5281/zenodo.22059963}
}