Peterson PP, Liu Z

Nutrient sensing is important for cell growth, aging, and longevity. In Saccharomyces cerevisiae, Sch9, an AGC-family protein kinase, is a major nutrient sensing kinase homologous to mammalian Akt and S6 kinase. Sch9 integrates environmental cues with cell growth by functioning downstream of TORC1 and in parallel with the Ras/PKA pathway. ...

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Mutations in SCH9 lead to reduced cell growth in dextrose medium; however, reports on the ability of sch9? mutants to utilize non-fermentable carbon sources are inconsistent. Here we show that sch9? mutant strains cannot grow on non-fermentable carbon sources and rapidly accumulate suppressor mutations, which reverse growth defects of sch9? mutants. sch9? induces gene expression of three transcription factors required for utilization of non-fermentable carbon sources, Cat8, Adr1, and Hap4, while sch9? suppressor mutations, termed sns1 and sns2, strongly decrease the gene expression of those transcription factors. Despite the genetic suppression interactions, both sch9? and sns1 (or sns2) homozygous mutants have severe defects in meiosis. By screening mutants defective in sporulation, we identified additional sch9? suppressor mutants with mutations in GPB1, GPB2, and MCK1. Using library complementation and genetic analysis, we identified SNS1 and SNS2 to be IRA2 and IRA1, respectively. Furthermore, we discovered that lifespan extension in sch9? mutants is dependent on IRA2 and that PKA inactivation greatly increases basal expression of CAT8, ADR1, and HAP4. Our results demonstrate that sch9? leads to complete loss of growth on non-fermentable carbon sources and mutations in MCK1 or genes encoding negative regulators of the Ras/PKA pathway reverse sch9? mutant phenotypes.

Date: Apr. 26, 2021

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