Integration of general amino acid control and Target of Rapamycin (TOR) regulatory pathways in nitrogen assimilation in yeast

Kirk A. Staschke, Souvik Dey, John M. Zaborske, Lakshmi Reddy Palam, Jeanette McClintick, Tao Pan, Howard Edenberg, Ronald Wek

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Two important nutrient-sensing and regulatory pathways, the general amino acid control (GAAC) and the target of rapamycin (TOR), participate in the control of yeast growth and metabolism during changes in nutrient availability. Amino acid starvation activates the GAAC through Gcn2p phosphorylation of translation factor eIF2 and preferential translation of GCN4, a transcription activator. TOR senses nitrogen availability and regulates transcription factors such as Gln3p. We used microarray analyses to address the integration of the GAAC and TOR pathways in directing the yeast transcriptome during amino acid starvation and rapamycin treatment. We found that GAAC is a major effector of the TOR pathway, with Gcn4p and Gln3p each inducing a similar number of genes during rapamycin treatment. Although Gcn4p activates a common core of 57 genes, the GAAC directs significant variations in the transcriptome during different stresses. In addition to inducing amino acid biosynthetic genes, Gcn4p in conjunction with Gln3p activates genes required for the assimilation of secondary nitrogen sources such as γ-aminobutyric acid (GABA). Gcn2p activation upon shifting to secondary nitrogen sources is suggested to occur by means of a dual mechanism. First, Gcn2p is induced by the release of TOR repression through a mechanism involving Sit4p protein phosphatase. Second, this eIF2 kinase is activated by select uncharged tRNAs, which were shown to accumulate during the shift to the GABA medium. This study highlights the mechanisms by which the GAAC and TOR pathways are integrated to recognize changing nitrogen availability and direct the transcriptome for optimal growth adaptation.

Original languageEnglish
Pages (from-to)16893-16911
Number of pages19
JournalJournal of Biological Chemistry
Volume285
Issue number22
DOIs
StatePublished - May 28 2010

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Sirolimus
Yeast
Nitrogen
Yeasts
Amino Acids
Genes
Transcriptome
Availability
Starvation
gamma-Aminobutyric Acid
Nutrients
Aminobutyrates
Food
Phosphorylation
Phosphoprotein Phosphatases
Transcription
Microarray Analysis
Microarrays
Growth
Transfer RNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Integration of general amino acid control and Target of Rapamycin (TOR) regulatory pathways in nitrogen assimilation in yeast. / Staschke, Kirk A.; Dey, Souvik; Zaborske, John M.; Palam, Lakshmi Reddy; McClintick, Jeanette; Pan, Tao; Edenberg, Howard; Wek, Ronald.

In: Journal of Biological Chemistry, Vol. 285, No. 22, 28.05.2010, p. 16893-16911.

Research output: Contribution to journalArticle

Staschke, Kirk A. ; Dey, Souvik ; Zaborske, John M. ; Palam, Lakshmi Reddy ; McClintick, Jeanette ; Pan, Tao ; Edenberg, Howard ; Wek, Ronald. / Integration of general amino acid control and Target of Rapamycin (TOR) regulatory pathways in nitrogen assimilation in yeast. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 22. pp. 16893-16911.
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