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Background

Cell growth and cell-cycle progression are tightly coordinated to enable cells to adjust their size (timing of division) to the demands of proliferation in varying nutritional environments. In fission yeast, nitrogen stress results in sustained proliferation at a reduced size.

Results

Here, we show that cells can sense nitrogen stress to reduce target of rapamycin complex-1 (TORC1) activity. Nitrogen-stress-induced TORC1 inhibition differs from amino-acid-dependent control of TORC1 and requires the Ssp2 (AMPKα) kinase, the Tsc1/2 complex, and Rhb1 GTPase. Importantly, the β and γ regulatory subunits of AMPK are not required to control cell division in response to nitrogen stress, providing evidence for a nitrogen-sensing mechanism that is independent of changes in intracellular ATP/AMP levels. The CaMKK homolog Ssp1 is constitutively required for phosphorylation of the AMPKα(Ssp2) T loop. However, we find that a second homolog CaMKK(Ppk34) is specifically required to stimulate AMPKα(Ssp2) activation in response to nitrogen stress. Finally, ammonia also controls mTORC1 activity in human cells; mTORC1 is activated upon the addition of ammonium to glutamine-starved Hep3B cancer cells.

Conclusions

The alternative nitrogen source ammonia can simulate TORC1 activity to support growth and division under challenging nutrient settings, a situation often seen in cancer."xsd:string
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http://purl.uniprot.org/citations/25639242http://purl.uniprot.org/core/author"Petersen J."xsd:string
http://purl.uniprot.org/citations/25639242http://purl.uniprot.org/core/author"Forte G.M."xsd:string
http://purl.uniprot.org/citations/25639242http://purl.uniprot.org/core/author"Davie E."xsd:string
http://purl.uniprot.org/citations/25639242http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25639242http://purl.uniprot.org/core/name"Curr Biol"xsd:string
http://purl.uniprot.org/citations/25639242http://purl.uniprot.org/core/pages"445-454"xsd:string
http://purl.uniprot.org/citations/25639242http://purl.uniprot.org/core/title"Nitrogen regulates AMPK to control TORC1 signaling."xsd:string
http://purl.uniprot.org/citations/25639242http://purl.uniprot.org/core/volume"25"xsd:string
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