title: Ubiquitin regulates TORC1 in yeast Saccharomyces cerevisiae.
abstract: In the yeast Saccharomyces cerevisiae the TOR complex 1 (TORC1) controls many growth-related cellular processes and is essential for cell growth and proliferation. Macrolide antibiotic rapamycin, in complex with a cytosol protein named FKBP12, specifically inhibits TORC1, causing growth arrest. The FKBP12-rapamycin complex interferes with TORC1 function by binding to the FRB domain of the TOR proteins. In an attempt to understand the role of the FRB domain in TOR function, we identified a single point mutation (Tor2(W2041R) ) in the FRB domain of Tor2 that renders yeast cells rapamycin resistant and temperature sensitive. At the permissive temperature, the Tor2 mutant protein is partially defective for binding with Kog1 and TORC1 is impaired for membrane association. At the restrictive temperature, Kog1 but not the Tor2 mutant protein, is rapidly degraded. Overexpression of ubiquitin stabilizes Kog1 and suppresses the growth defect associated with the tor2 mutant at the nonpremissive temperature. We find that ubiquitin binds non-covalently to Kog1, prevents Kog1 from degradation and stabilizes TORC1. Our data reveal a unique role for ubiquitin in regulation of TORC1 and suggest that Kog1 requires association with the Tor proteins for stabilization.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
authors.forename: Kejin
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Biology, Henan University, Kaifeng, 475000, China.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
authors.forename: Gonghong
authors.initials: G
authors.lastname: Yan
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, 116024, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Medical and Healthcare Center, Hainan Provincial People's Hospital, Haikou, 570311, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D008565:Membrane Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: C515118:Kog1 protein, S cerevisiae; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D017853:Phosphotransferases (Alcohol Group Acceptor); D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus