TORC1 signaling is governed by two negative regulators in fission yeast.
The target of rapamycin (TOR) is a highly conserved protein kinase that regulates cell growth and metabolism. Here we performed a genome-wide screen to identify negative regulators of TOR complex 1 (TORC1) in Schizosaccharomyces pombe by isolating mutants that phenocopy Δtsc2, in which TORC1 signaling is known to be up-regulated. We discovered that Δnpr2 displayed similar phenotypes to Δtsc2 in terms of amino acid uptake defects and mislocalization of the Cat1 permease. However, Δnpr2 and Δtsc2 clearly showed different phenotypes in terms of rapamycin supersensitivity and Isp5 transcription upon various treatments. Furthermore, we showed that Tor2 controls amino acid homeostasis at the transcriptional and post-transcriptional levels. Our data reveal that both Npr2 and Tsc2 negatively regulate TORC1 signaling, and Npr2, but not Tsc2, may be involved in the feedback loop of a nutrient-sensing pathway.
Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Ning
N
Ma
Qingbin
Q
Liu
Lili
L
Zhang
Elizabeth P
EP
Henske
Yan
Y
Ma
D000595:Amino Acid Sequence; D026905:Amino Acid Transport Systems / Q000378:metabolism; D000596:Amino Acids / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D015966:Gene Expression Regulation, Fungal; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
D026905:Amino Acid Transport Systems; D000596:Amino Acids; C530694:Cat1 protein, S pombe; D046912:Multiprotein Complexes; D029702:Schizosaccharomyces pombe Proteins; C471573:Tsc2 protein, S pombe; C588354:npr2 protein, S pombe; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D017461:Receptors, Atrial Natriuretic Factor
Npr2; TORC1; Tor2; Tsc2; nutrient response