TORC1 controls degradation of the transcription factor Stp1, a key effector of the SPS amino-acid-sensing pathway in Saccharomyces cerevisiae.
The target of rapamycin (TOR) signaling pathway plays crucial roles in the regulation of eukaryotic cell growth. In Saccharomyces cerevisiae, nitrogen sources in the extracellular environment activate the TOR signaling pathway. However, the precise mechanisms underlying the regulation of TOR activity in response to extracellular nitrogen sources are poorly understood. Here, we report that degradation of Stp1, a transcription factor for amino acid uptake and a key effector of the SPS amino-acid-sensing pathway, is controlled by TOR activity in S. cerevisiae. Using a genome-wide protein localization study, we found that Stp1 disappeared from the nucleus upon inactivation of TOR complex 1 (TORC1) by rapamycin, suggesting the involvement of Stp1 in the TOR signaling pathway. Supporting this notion, a knockout mutant for the STP1 gene was found to be hypersensitive to rapamycin, and overexpression of STP1 conferred resistance to rapamycin. Interestingly, we found that the rapamycin-induced disappearance of Stp1 from the nucleus resulted from Stp1 degradation, which was dependent on the activity of a protein phosphatase 2A (PP2A)-like phosphatase, Sit4, which is a well-known downstream effector of TORC1. Taken together, our findings highlight an intimate connection between the amino-acid-sensing pathway and the rapamycin-sensitive TOR signaling pathway.
Shin
Chun-Shik
CS
School of Biological Sciences and Research Center for Functional Cellulomics, Institute of Microbiology, Seoul National University, Seoul 151-747, Republic of Korea.
Kim
Sun Young
SY
Huh
Won-Ki
WK
D000596:Amino Acids / Q000378:metabolism*; D000935:Antifungal Agents / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000235:genetics; D016681:Genome, Fungal / Q000187:drug effects; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D030781:Organisms, Genetically Modified; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000235:genetics; D053038:Quorum Sensing / Q000235:genetics / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000596:Amino Acids; D000935:Antifungal Agents; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C074632:STP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus