A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dubé syndrome.

Napolitano G, Di Malta C, Esposito A, de Araujo MEG, Pece S, Bertalot G, Matarese M, Benedetti V, Zampelli A, Stasyk T, Siciliano D, …, Ballabio A · 2020 · Nature · Atlas ID NAP2020

What this study shows

A substrate-specific mTORC1-TFEB pathway (RagC/D-dependent) drives Birt-Hogg-Dube kidney disease.

Abstract

ShowHide

The mechanistic target of rapamycin complex 1 (mTORC1) is a key metabolic hub that controls the cellular response to environmental cues by exerting its kinase activity on multiple substrates. However, whether mTORC1 responds to diverse stimuli by differentially phosphorylating specific substrates is poorly understood. Here we show that transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is phosphorylated by mTORC1 via a substrate-specific mechanism that is mediated by Rag GTPases.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cells; mouse) 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 type	5 - Mechanistic / In Vitro
Model system	Human cells; mouse
Journal	Nature
Year	2020
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/s41586-020-2444-0 · PMID 32612235 · Free full text (PMC7610377)

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 (FLCN / mTORC1)
Target	mTORC1 / TFEB / FLCN
Model	Human cells; mouse
Effect	A substrate-specific mTORC1 pathway phosphorylates TFEB and underlies Birt-Hogg-Dubé syndrome

In the Atlas

Links in the pathway map

Supports FLCN / FNIP1/2 activates Rag GTPases

Cite this paper

ShowHide

Napolitano, G., Di Malta, C., Esposito, A., de Araujo, M. E. G., Pece, S., Bertalot, G., Matarese, M., Benedetti, V., Zampelli, A., Stasyk, T., Siciliano, D., Venuta, A., Cesana, M., Vilardo, C., Nusco, E., Monfregola, J., Calcagnì, A., Di Fiore, P. P., Huber, L. A., & Ballabio, A. (2020). A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dubé syndrome. Nature. https://doi.org/10.1038/s41586-020-2444-0

@article{NAP2020,
  author       = {Napolitano, G. and Di Malta, C. and Esposito, A. and de Araujo, M. E. G. and Pece, S. and Bertalot, G. and Matarese, M. and Benedetti, V. and Zampelli, A. and Stasyk, T. and Siciliano, D. and Venuta, A. and Cesana, M. and Vilardo, C. and Nusco, E. and Monfregola, J. and Calcagnì, A. and Di Fiore, P. P. and Huber, L. A. and Ballabio, A.},
  title        = {{A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dubé syndrome}},
  journal      = {Nature},
  year         = {2020},
  doi          = {10.1038/s41586-020-2444-0},
  note         = {PMID: 32612235},
}

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 NAP2020) [Data set]. https://mtor-atlas.org/study/NAP2020/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_NAP2020,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record NAP2020},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/NAP2020/},
  doi          = {10.5281/zenodo.22059963}
}

Was this page useful?