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mTOR-dependent phosphorylation controls TFEB nuclear export

Napolitano, Gennaro, Esposito, Alessandra, Choi, Heejun, Matarese, Maria, Benedetti, Valerio, Di Malta, Chiara, Monfregola, Jlenia, Medina, Diego Luis, Lippincott-Schwartz, Jennifer, Ballabio, Andrea·2018·Nature Communications
DOI 10.1038/s41467-018-05862-6PMC PMC6098152

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Abstract

During starvation the transcriptional activation of catabolic processes is induced by the nuclear translocation and consequent activation of transcription factor EB (TFEB), a master modulator of autophagy and lysosomal biogenesis. However, how TFEB is inactivated upon nutrient refeeding is currently unknown. Here we show that TFEB subcellular localization is dynamically controlled by its continuous shuttling between the cytosol and the nucleus, with the nuclear export representing a limiting step. TFEB nuclear export is mediated by CRM1 and is modulated by nutrient availability via mTOR-dependent hierarchical multisite phosphorylation of serines S142 and S138, which are localized in proximity of a nuclear export signal (NES). Our data on TFEB nucleo-cytoplasmic shuttling suggest an unpredicted role of mTOR in nuclear export.

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Crossref · 10.1038/s41467-018-05862-6

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  • An AMPK-SKP2-CARM1 signaling cascade plays a role in transcriptional regulation of autophagy, and CARM1 exerts a transcriptional coactivator function on autophagy and lysosomal genes through TFEB.

    “Finally, an AMPK-SKP2-CARM1 signaling cascade has also been reported to play a role in transcriptional regulation of autophagy [974]; CARM1 exerts a transcriptional coactivator function on autophagy and lysosomal genes through TFEB.”

    From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [974]

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Citations

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Research works printed but not linked: 37

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Metadata

Authors
Napolitano, G., Esposito, A., Choi, H., Matarese, M., Benedetti, V., Di Malta, C., Monfregola, J., Medina, D. L., Lippincott-Schwartz, J., & Ballabio, A.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-08-17
Volume
9
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-018-05862-6
PMC
PMC6098152
Cited by
406
References
2
Language
en
Licence

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