ArticleMolecular biology of the cell2011
A phosphodegron controls nutrient-induced proteasomal activation of the signaling protease Ssy5.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Structural bases of signal generation and transduction by the SPS amino acid sensor of Saccharomyces cerevisiae.G3 (Bethesda, Md.) · 2026Article
- The Molecular Basis of Amino Acids Sensing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- A dual reporter system for intracellular and extracellular amino acid sensing in budding yeast.Molecular biology of the cell · 2025Article
- Contribution of proteases to the hallmarks of aging and to age-related neurodegeneration.Aging cell · 2022Review
- Inner Nuclear Membrane Asi Ubiquitin Ligase Catalytic Subunits Asi1p and Asi3p, but not Asi2p, confer resistance to aminoglycoside hygromycin B inmicroPublication biology · 2021Article
- Spatial and temporal regulation of the endoproteolytic activity of the SPS-sensor-controlled Ssy5 signaling protease.Molecular biology of the cell · 2019Article
- Ssy5 is a signaling serine protease that exhibits atypical biogenesis and marked S1 specificity.The Journal of biological chemistry · 2018Article
- Regulation of Sensing, Transportation, and Catabolism of Nitrogen Sources in Saccharomyces cerevisiae.Microbiology and molecular biology reviews : MMBR · 2018Review
- A reference-based protein degradation assay without global translation inhibitors.The Journal of biological chemistry · 2017Article
- Nutrient Sensing at the Plasma Membrane of Fungal Cells.Microbiology spectrum · 2017Review
- Nutrient sensing and TOR signaling in yeast and mammals.The EMBO journal · 2017Review
- The SPS amino acid sensor mediates nutrient acquisition and immune evasion in Candida albicans.Cellular microbiology · 2016Article
- Less is more: Nutrient limitation induces cross-talk of nutrient sensing pathways with NADFrontiers in biology · 2015Article
- Reduced Ssy1-Ptr3-Ssy5 (SPS) signaling extends replicative life span by enhancing NAD+ homeostasis in Saccharomyces cerevisiae.The Journal of biological chemistry · 2015Article
- Review
- Latency of transcription factor Stp1 depends on a modular regulatory motif that functions as cytoplasmic retention determinant and nuclear degron.Molecular biology of the cell · 2014Article
- Nutrient sensing and signaling in the yeast Saccharomyces cerevisiae.FEMS microbiology reviews · 2014Review
- Rts1-protein phosphatase 2A antagonizes Ptr3-mediated activation of the signaling protease Ssy5 by casein kinase I.Molecular biology of the cell · 2013Article
- Hsp70 nucleotide exchange factor Fes1 is essential for ubiquitin-dependent degradation of misfolded cytosolic proteins.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Regulation of amino acid, nucleotide, and phosphate metabolism in Saccharomyces cerevisiae.Genetics · 2012Article
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4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulated proteolysis serves as a mechanism to control cellular processes. The SPS (Ssy1-Ptr3-Ssy5) sensor in yeast responds to extracellular amino acids by endoproteolytically activating transcription factors Stp1 and Stp2 (Stp1/2). The processing endoprotease Ssy5 is regulated via proteasomal degradation of its noncovalently associated N-terminal prodomain. We find that degradation of the prodomain requires a conserved phosphodegron comprising phosphoacceptor sites and ubiquitin-accepting lysine residues. Upon amino acid induction, the phosphodegron is modified in a series of linked events by a set of general regulatory factors involved in diverse signaling pathways. First, an amino acid-induced conformational change triggers phosphodegron phosphorylation by the constitutively active plasma membrane-localized casein kinase I (Yck1/2). Next the prodomain becomes a substrate for polyubiquitylation by the Skp1/Cullin/Grr1 E3 ubiquitin ligase complex (SCF(Grr1)). Finally, the modified prodomain is concomitantly degraded by the 26S proteasome. These integrated events are requisite for unfettering the Ssy5 endoprotease, and thus Stp1/2 processing. The Ssy5 phosphoacceptor motif resembles the Yck1/2- and Grr1-dependent degrons of regulators in the Snf3/Rgt2 glucose-sensing pathway. Our work defines a novel proteolytic activation cascade that regulates an intracellular signaling protease and illustrates how general signaling components are recruited to distinct pathways that achieve conditional and specific signaling outputs.
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