Ubiquitin regulates TORC1 in yeast Saccharomyces cerevisiae

Kejin Hu1, Shuguang Guo2, Gonghong Yan1

  • 1Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.

Molecular Microbiology
|December 25, 2015
PubMed

Insights

A mutation in yeast

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The TOR complex 1 (TORC1) in Saccharomyces cerevisiae regulates cell growth and proliferation.
  • Rapamycin, complexed with FKBP12, inhibits TORC1 by binding to its FRB domain, leading to growth arrest.

Purpose of the Study:

  • To investigate the role of the FRB domain in TOR protein function.
  • To understand the mechanism of rapamycin resistance and temperature sensitivity in yeast mutants.

Main Methods:

  • Identification of a point mutation (Tor2(W2041R)) in the FRB domain of Tor2.
  • Analysis of yeast cell growth, protein binding, membrane association, and degradation at different temperatures.
  • Investigating the effect of ubiquitin overexpression on Kog1 stability and TORC1 function.

Main Results:

  • The Tor2(W2041R) mutation confers rapamycin resistance and temperature sensitivity.
  • The mutant protein shows impaired binding with Kog1 and reduced TORC1 membrane association.
  • At restrictive temperatures, Kog1 is degraded, but ubiquitin overexpression stabilizes Kog1 and rescues growth defects.

Conclusions:

  • Ubiquitin plays a novel role in regulating TORC1 by non-covalently binding to Kog1 and preventing its degradation.
  • Kog1 stabilization is crucial for TORC1 function and requires association with Tor proteins.
  • The FRB domain is critical for TORC1 stability and cellular growth regulation.

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