TORC1 and TORC2 converge to regulate the SAGA co-activator in response to nutrient availability

Thomas Laboucarié, Dylane Detilleux, Ricard Rodriguez-Mias, Céline Faux, Yves Romeo, Mirita Franz-Wachtel, Karsten Krug, Boris Macek, Judit Villén, Janni Petersen, Dominique Helmlinger

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    15 Citations (Scopus)

    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 Gad8AKT 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.

    Original languageEnglish
    Pages (from-to)2197-2218
    Number of pages22
    JournalEMBO REPORTS
    Volume18
    Issue number12
    DOIs
    Publication statusPublished - 2017

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    Laboucarié, T., Detilleux, D., Rodriguez-Mias, R., Faux, C., Romeo, Y., Franz-Wachtel, M., Krug, K., Macek, B., Villén, J., Petersen, J., & Helmlinger, D. (2017). TORC1 and TORC2 converge to regulate the SAGA co-activator in response to nutrient availability. EMBO REPORTS, 18(12), 2197-2218. https://doi.org/10.15252/embr.201744942