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Cited by 28Fungal and yeast genetics researchPI3K/AKT/mTOR signaling in cancerBacterial Genetics and Biotechnology

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Sit4 and PP2A Dephosphorylate Nitrogen Catabolite Repression-Sensitive Gln3 When TorC1 Is Up- as Well as Downregulated

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Tate, Jennifer J, Tolley, Elizabeth A, Cooper, Terrance G·2019·Genetics
DOI 10.1534/genetics.119.302371PMC PMC6707456
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Abstract

Saccharomyces cerevisiae lives in boom and bust nutritional environments. Sophisticated regulatory systems have evolved to rapidly cope with these changes while preserving intracellular homeostasis. Target of Rapamycin Complex 1 (TorC1), is a serine/threonine kinase complex and a principle nitrogen-responsive regulator. TorC1 is activated by excess nitrogen and downregulated by limiting nitrogen. Two of TorC1’s many downstream targets are Gln3 and Gat1—GATA-family transcription activators—whose localization and function are Nitrogen Catabolite Repression- (NCR-) sensitive. In nitrogen replete environments, TorC1 is activated, thereby inhibiting the PTap42-Sit4 and PTap42-PP2A (Pph21/Pph22-Tpd3, Pph21,22-Rts1/Cdc55) phosphatase complexes. Gln3 is phosphorylated, sequestered in the cytoplasm and NCR-sensitive transcription repressed. In nitrogen-limiting conditions, TorC1 is downregulated and PTap42-Sit4 and PTap42-PP2A are active. They dephosphorylate Gln3, which dissociates from Ure2, relocates to the nucleus, and activates transcription. A paradoxical observation, however, led us to suspect that Gln3 control was more complex than appreciated, i.e., Sit4 dephosphorylates Gln3 more in excess than in limiting nitrogen conditions. This paradox motivated us to reinvestigate the roles of these phosphatases in Gln3 regulation. We discovered that: (i) Sit4 and PP2A actively function both in conditions where TorC1 is activated as well as down-regulated; (ii) nuclear Gln3 is more highly phosphorylated than when it is sequestered in the cytoplasm; (iii) in nitrogen-replete conditions, Gln3 relocates from the nucleus to the cytoplasm, where it is dephosphorylated by Sit4 and PP2A; and (iv) in nitrogen excess and limiting conditions, Sit4, PP2A, and Ure2 are all required to maintain cytoplasmic Gln3 in its dephosphorylated form.

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  • The transcription factor Gln3 plays a crucial role in regulating nitrogen and carbon metabolisms during yeast fermentation; the nitrogen-induced TORC1 complex, along with regulation of carbon catabolite repression, activates the kinase Snf1 to ensure proper metabolic activity in yeast.

    “The transcription factor Gln3 plays a crucial role in regulating nitrogen and carbon metabolisms during yeast fermentation. The nitrogen-induced TORC1 complex, along with the regulation of carbon catabolite repression, activates the kinase Snf1 to ensure proper metabolic activity in yeast [51,52].”

    From The Metabolic Pathways of Yeast and Acetic Acid Bacteria During Fruit Vinegar Fermentation and Their Influence on Flavor Development (2025) · cites this paper as [52]

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Metadata

Authors
Tate, J. J., Tolley, E. A., & Cooper, T. G.
Affiliations
University of Tennessee Health Science Center (US)
Corresponding author
Cooper, Terrance G
ORCID
Venue
Genetics
Publisher
Oxford University Press (OUP)
Published
2019-06-18
Volume
212
Issue
4
Pages
1205-1225
ISSN
  • 0016-6731 (ISSN-L)
  • 1943-2631
DOI
10.1534/genetics.119.302371
PMC
PMC6707456
OpenAlex
W2950520052
Cited by
28
References
0
Citations by year
2026: 2 · 2025: 3 · 2024: 11 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 1
FWCI
0.66
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • Health Science Center, University of Tennessee
  • National Institute of General Medical Sciences (R01GM035642)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
Sit4, protein phosphatase 2A, Gln3, TORC1, nitrogen catabolite repression, nitrogen signaling, GATA transcription factors, Ure2, protein dephosphorylation, phosphatase regulation, nuclear-cytoplasmic localization, Saccharomyces cerevisiae
MeSH terms
Mechanistic Target of Rapamycin Complex 1, Cell Nucleus, Glutathione Peroxidase, Nitrogen, Phosphorylation, Prions, Saccharomyces cerevisiae, Transcription Factors, Active Transport, Cell Nucleus, Saccharomyces cerevisiae Proteins, Protein Phosphatase 2, Catabolite Repression

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