TORC1 and TORC2 converge to regulate the SAGA co-activator in response to nutrient availability.
Identifieur interne : 000306 ( Main/Exploration ); précédent : 000305; suivant : 000307TORC1 and TORC2 converge to regulate the SAGA co-activator in response to nutrient availability.
Auteurs : Thomas Laboucarié [France] ; Dylane Detilleux [France] ; Ricard A. Rodriguez-Mias [États-Unis] ; Céline Faux [France] ; Yves Romeo [France] ; Mirita Franz-Wachtel [Allemagne] ; Karsten Krug [Allemagne] ; Boris Ma Ek [Allemagne] ; Judit Villén [États-Unis] ; Janni Petersen [Australie] ; Dominique Helmlinger [France]Source :
- EMBO reports [ 1469-3178 ] ; 2017.
Abstract
Gene expression regulation is essential for cells to adapt to changes in their environment. Co-activator complexes have well-established roles in transcriptional regulation, but less is known about how they sense and respond to signaling cues. We have previously shown that, in fission yeast, one such co-activator, the SAGA complex, controls gene expression and the switch from proliferation to differentiation in response to nutrient availability. Here, using a combination of genetic, biochemical, and proteomic approaches, we show that SAGA responds to nutrients through the differential phosphorylation of its Taf12 component, downstream of both the TORC1 and TORC2 pathways. Taf12 phosphorylation increases early upon starvation and is controlled by the opposing activities of the PP2A phosphatase, which is activated by TORC1, and the TORC2-activated Gad8(AKT) kinase. Mutational analyses suggest that Taf12 phosphorylation prevents cells from committing to differentiation until starvation reaches a critical level. Overall, our work reveals that SAGA is a direct target of nutrient-sensing pathways and has uncovered a mechanism by which TORC1 and TORC2 converge to control gene expression and cell fate decisions.
DOI: 10.15252/embr.201744942
PubMed: 29079657
Affiliations:
- Allemagne, Australie, France, États-Unis
- Bade-Wurtemberg, District de Tübingen, Languedoc-Roussillon, Occitanie (région administrative), Washington (État)
- Montpellier, Seattle, Tübingen
- Université de Washington
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region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Romeo, Yves" sort="Romeo, Yves" uniqKey="Romeo Y" first="Yves" last="Romeo">Yves Romeo</name><affiliation wicri:level="3"><nlm:affiliation>CRBM, CNRS, University of Montpellier, Montpellier, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRBM, CNRS, University of Montpellier, Montpellier</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Franz Wachtel, Mirita" sort="Franz Wachtel, Mirita" uniqKey="Franz Wachtel M" first="Mirita" last="Franz-Wachtel">Mirita Franz-Wachtel</name><affiliation wicri:level="3"><nlm:affiliation>Proteome Center Tübingen, Tuebingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Proteome Center Tübingen, Tuebingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation></author><author><name sortKey="Krug, Karsten" sort="Krug, Karsten" uniqKey="Krug K" first="Karsten" last="Krug">Karsten Krug</name><affiliation wicri:level="3"><nlm:affiliation>Proteome Center Tübingen, Tuebingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Proteome Center Tübingen, Tuebingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation></author><author><name sortKey="Ma Ek, Boris" sort="Ma Ek, Boris" uniqKey="Ma Ek B" first="Boris" last="Ma Ek">Boris Ma Ek</name><affiliation wicri:level="3"><nlm:affiliation>Proteome Center Tübingen, Tuebingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Proteome Center Tübingen, Tuebingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation></author><author><name sortKey="Villen, Judit" sort="Villen, Judit" uniqKey="Villen J" first="Judit" last="Villén">Judit Villén</name><affiliation wicri:level="4"><nlm:affiliation>Department of Genome Sciences, University of Washington, Seattle, WA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genome Sciences, University of Washington, Seattle, WA</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Petersen, Janni" sort="Petersen, Janni" uniqKey="Petersen J" first="Janni" last="Petersen">Janni Petersen</name><affiliation wicri:level="1"><nlm:affiliation>Flinders Centre for Innovation in Cancer, School of Medicine, Faculty of Health Science, Flinders University, Adelaide, SA, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Flinders Centre for Innovation in Cancer, School of Medicine, Faculty of Health Science, Flinders University, Adelaide, SA</wicri:regionArea><wicri:noRegion>SA</wicri:noRegion></affiliation></author><author><name sortKey="Helmlinger, Dominique" sort="Helmlinger, Dominique" uniqKey="Helmlinger D" first="Dominique" last="Helmlinger">Dominique Helmlinger</name><affiliation wicri:level="3"><nlm:affiliation>CRBM, CNRS, University of Montpellier, Montpellier, France dhelmlinger@crbm.cnrs.fr.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>CRBM, CNRS, University of Montpellier, Montpellier</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author></analytic><series><title level="j">EMBO reports</title><idno type="eISSN">1469-3178</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Gene expression regulation is essential for cells to adapt to changes in their environment. Co-activator complexes have well-established roles in transcriptional regulation, but less is known about how they sense and respond to signaling cues. We have previously shown that, in fission yeast, one such co-activator, the SAGA complex, controls gene expression and the switch from proliferation to differentiation in response to nutrient availability. Here, using a combination of genetic, biochemical, and proteomic approaches, we show that SAGA responds to nutrients through the differential phosphorylation of its Taf12 component, downstream of both the TORC1 and TORC2 pathways. Taf12 phosphorylation increases early upon starvation and is controlled by the opposing activities of the PP2A phosphatase, which is activated by TORC1, and the TORC2-activated Gad8(AKT) kinase. Mutational analyses suggest that Taf12 phosphorylation prevents cells from committing to differentiation until starvation reaches a critical level. Overall, our work reveals that SAGA is a direct target of nutrient-sensing pathways and has uncovered a mechanism by which TORC1 and TORC2 converge to control gene expression and cell fate decisions.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>États-Unis</li></country><region><li>Bade-Wurtemberg</li><li>District de Tübingen</li><li>Languedoc-Roussillon</li><li>Occitanie (région administrative)</li><li>Washington (État)</li></region><settlement><li>Montpellier</li><li>Seattle</li><li>Tübingen</li></settlement><orgName><li>Université de Washington</li></orgName></list><tree><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Laboucarie, Thomas" sort="Laboucarie, Thomas" uniqKey="Laboucarie T" first="Thomas" last="Laboucarié">Thomas Laboucarié</name></region><name sortKey="Detilleux, Dylane" sort="Detilleux, Dylane" uniqKey="Detilleux D" first="Dylane" last="Detilleux">Dylane Detilleux</name><name sortKey="Faux, Celine" sort="Faux, Celine" uniqKey="Faux C" first="Céline" last="Faux">Céline Faux</name><name sortKey="Helmlinger, Dominique" sort="Helmlinger, Dominique" uniqKey="Helmlinger D" first="Dominique" last="Helmlinger">Dominique Helmlinger</name><name sortKey="Romeo, Yves" sort="Romeo, Yves" uniqKey="Romeo Y" first="Yves" last="Romeo">Yves Romeo</name></country><country name="États-Unis"><region name="Washington (État)"><name sortKey="Rodriguez Mias, Ricard A" sort="Rodriguez Mias, Ricard A" uniqKey="Rodriguez Mias R" first="Ricard A" last="Rodriguez-Mias">Ricard A. Rodriguez-Mias</name></region><name sortKey="Villen, Judit" sort="Villen, Judit" uniqKey="Villen J" first="Judit" last="Villén">Judit Villén</name></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Franz Wachtel, Mirita" sort="Franz Wachtel, Mirita" uniqKey="Franz Wachtel M" first="Mirita" last="Franz-Wachtel">Mirita Franz-Wachtel</name></region><name sortKey="Krug, Karsten" sort="Krug, Karsten" uniqKey="Krug K" first="Karsten" last="Krug">Karsten Krug</name><name sortKey="Ma Ek, Boris" sort="Ma Ek, Boris" uniqKey="Ma Ek B" first="Boris" last="Ma Ek">Boris Ma Ek</name></country><country name="Australie"><noRegion><name sortKey="Petersen, Janni" sort="Petersen, Janni" uniqKey="Petersen J" first="Janni" last="Petersen">Janni Petersen</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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