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Mks1 in concert with TOR signaling negatively regulates RTG target gene expression in S. cerevisiae

Ivanka Dilova1, Ching-Yi Chen, Ted Powers

  • 1Section of Molecular and Cellular Biology and Center for Genetics and Development, Division of Biological Sciences, University of California, Davis 95616, USA.

Current Biology : CB
|March 8, 2002
PubMed

Insights

The target of rapamycin (TOR) pathway regulates cell growth using Rtg2 and Mks1 proteins. Mks1 is a negative regulator of amino acid biosynthesis genes, and its activity is controlled by TOR signaling.

Area of Science:

  • Cellular biology
  • Molecular genetics
  • Biochemistry

Background:

  • The target of rapamycin (TOR) pathway is crucial for eukaryotic cell growth regulation in response to nutrient availability.
  • TOR signaling influences gene expression in nutrient-responsive biosynthetic pathways in Saccharomyces cerevisiae.
  • TOR regulates the subcellular localization of the Rtg1/Rtg3 transcription factor complex, impacting gene expression.

Purpose of the Study:

  • To elucidate the function of the Rtg2 protein in TOR signaling.
  • To identify and characterize the role of Mks1 as a regulator of RTG target genes.
  • To understand the complex regulatory network within this branch of TOR signaling.

Main Methods:

  • Epistasis analyses were performed to determine the order of action of TOR, Rtg2, Mks1, Rtg1, and Rtg3.
  • Protein phosphorylation was analyzed to understand the regulation of Mks1.
  • Microarray analysis was used to identify genes regulated by Mks1 and the RTG pathway.

Main Results:

  • Rtg2 antagonizes the activity of Mks1, a negative regulator of RTG target gene activation.
  • Mks1 and Rtg2 act downstream of TOR and upstream of the Rtg1/Rtg3 transcription factors.
  • Mks1 phosphorylation is responsive to TOR and Rtg1/Rtg3 proteins, indicating complex regulation.
  • Microarray analysis revealed that lysine biosynthetic genes are robustly expressed in mks1Δ cells, dependent on the RTG pathway.

Conclusions:

  • Rtg2 functions by antagonizing Mks1, a key negative regulator in the TOR-controlled amino acid biosynthesis pathway.
  • The study clarifies the roles of Rtg2 and Mks1 in TOR signaling and their interaction with the Rtg1/Rtg3 complex.
  • Mks1 is identified as a crucial link between TOR signaling and the regulation of amino acid and lysine biosynthesis.

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