A TFEB nuclear export signal integrates amino acid supply and glucose availability

Linxin Li, Hans J. Friedrichsen, Sarah Andrews, Sarah Picaud, Laurent Volpon, Kaochin Ngeow, Georgina Berridge, Roman Fischer, Katherine L. B. Borden, Panagis Filippakopoulos and Colin R. Goding ()
Additional contact information
Linxin Li: University of Oxford
Hans J. Friedrichsen: University of Oxford
Sarah Andrews: University of Oxford
Sarah Picaud: University of Oxford
Laurent Volpon: Université de Montréal, Pavillon Marcel-Coutou, Chemin de la Polytechnique
Kaochin Ngeow: University of Oxford
Georgina Berridge: University of Oxford
Roman Fischer: University of Oxford
Katherine L. B. Borden: Université de Montréal, Pavillon Marcel-Coutou, Chemin de la Polytechnique
Panagis Filippakopoulos: University of Oxford
Colin R. Goding: University of Oxford

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract How cells coordinate the response to fluctuating carbon and nitrogen availability required to maintain effective homeostasis is a key issue. Amino acid limitation that inactivates mTORC1 promotes de-phosphorylation and nuclear translocation of Transcription Factor EB (TFEB), a key transcriptional regulator of lysosome biogenesis and autophagy that is deregulated in cancer and neurodegeneration. Beyond its cytoplasmic sequestration, how TFEB phosphorylation regulates its nuclear-cytoplasmic shuttling, and whether TFEB can coordinate amino acid supply with glucose availability is poorly understood. Here we show that TFEB phosphorylation on S142 primes for GSK3β phosphorylation on S138, and that phosphorylation of both sites but not either alone activates a previously unrecognized nuclear export signal (NES). Importantly, GSK3β is inactivated by AKT in response to mTORC2 signaling triggered by glucose limitation. Remarkably therefore, the TFEB NES integrates carbon (glucose) and nitrogen (amino acid) availability by controlling TFEB flux through a nuclear import-export cycle.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-04849-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04849-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-04849-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().