Abstract
In Saccharomyces cerevisiae, the TEA transcription factor Tec1 controls several developmental programs in response to nutrients and pheromones. Tec1 is targeted by the pheromone-responsive Fus3/Kss1 mitogen-activated protein kinase (MAPK) cascade, which destabilizes the transcription factor to ensure efficient mating of sexual partner cells. The regulation of Tec1 by signaling pathways that control cell division and development in response to nutrients, however, is not known. Here, we show that Tec1 protein stability is under control of the nutrient-sensitive target of rapamycin complex 1 (TORC1) signaling pathway via the Tip41-Tap42-Sit4 branch. We further show that degradation of Tec1 upon inhibition of TORC1 by rapamycin does not involve polyubiquitylation and appears to be proteasome independent. However, rapamycin-induced Tec1 degradation depends on the HECT ubiquitin ligase Rsp5, which physically interacts with Tec1 via conserved PxY motives. We further demonstrate that rapamycin and mating pheromone control Tec1 protein stability through distinct mechanisms by targeting different domains of the transcription factor. Finally, we show that Tec1 is a positive regulator of yeast chronological lifespan (CLS), a known TORC1-regulated process. Our findings indicate that in yeast, Tec1 links TORC1 and MAPK signaling pathways to coordinate control of cellular development in response to different stimuli.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Antifungal Agents / pharmacology
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Blotting, Northern
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Cyclins / genetics
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Cyclins / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Endosomal Sorting Complexes Required for Transport / genetics
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Endosomal Sorting Complexes Required for Transport / metabolism
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Gene Expression Regulation, Fungal / drug effects
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Immunoblotting
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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MAP Kinase Signaling System*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Microscopy, Fluorescence
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Protein Binding
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Protein Phosphatase 2 / genetics
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Protein Phosphatase 2 / metabolism
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / antagonists & inhibitors
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Sirolimus / pharmacology
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Two-Hybrid System Techniques
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Ubiquitin-Protein Ligase Complexes / genetics
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Ubiquitin-Protein Ligase Complexes / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Antifungal Agents
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CLN1 protein, S cerevisiae
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Cyclins
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DNA-Binding Proteins
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Endosomal Sorting Complexes Required for Transport
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FLO11 protein, S cerevisiae
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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Saccharomyces cerevisiae Proteins
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TAP42 protein, S cerevisiae
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TEC1 protein, S cerevisiae
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TIP41 protein, S cerevisiae
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TORC1 protein complex, S cerevisiae
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Transcription Factors
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Green Fluorescent Proteins
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Ubiquitin-Protein Ligase Complexes
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Protein Phosphatase 2
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SIT4 protein, S cerevisiae
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RSP5 protein, S cerevisiae
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Sirolimus