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Scientific article
Open access
English

Sfp1 interaction with TORC1 and Mrs6 reveals feedback regulation on TOR signaling

Published inMolecular cell, vol. 33, no. 6, p. 704-716
Publication date2009
Abstract

Ribosome biogenesis drives cell growth, and the large transcriptional output underlying this process is tightly regulated. The Target of Rapamycin (TOR) kinase is part of a highly conserved signaling pathway linking nutritional and stress signals to regulation of ribosomal protein (RP) and ribosome biogenesis (Ribi) gene transcription. In Saccharomyces cerevisiae, one of the downstream effectors of TOR is Sfp1, a transcriptional activator that regulates both RP and Ribi genes. Here, we report that Sfp1 interacts directly with TOR complex 1 (TORC1) in a rapamycin-regulated manner, and that phosphorylation of Sfp1 by this kinase complex regulates its function. Sfp1, in turn, negatively regulates TORC1 phosphorylation of Sch9, another key TORC1 target that acts in parallel with Sfp1, revealing a feedback mechanism controlling the activity of these proteins. Finally, we show that the Sfp1-interacting protein Mrs6, a Rab escort protein involved in membrane trafficking, regulates both Sfp1 nuclear localization and TORC1 signaling.

Keywords
  • Adaptor Proteins, Signal Transducing
  • Cell Nucleus/metabolism
  • Chromatin Immunoprecipitation
  • Cycloheximide/pharmacology
  • DNA-Binding Proteins/genetics/metabolism
  • Feedback, Physiological/physiology
  • Immunoprecipitation
  • Phosphorylation
  • Promoter Regions, Genetic/genetics
  • Protein-Serine-Threonine Kinases/genetics/metabolism
  • Saccharomyces cerevisiae/genetics/growth & development/metabolism
  • Saccharomyces cerevisiae Proteins/genetics/metabolism
  • Sirolimus/pharmacology
Citation (ISO format)
LEMPIAINEN, Harri et al. Sfp1 interaction with TORC1 and Mrs6 reveals feedback regulation on TOR signaling. In: Molecular cell, 2009, vol. 33, n° 6, p. 704–716. doi: 10.1016/j.molcel.2009.01.034
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Article (Published version)
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ISSN of the journal1097-4164
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