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A phosphodegron controls nutrient-induced proteasomal activation of the signaling protease Ssy5

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 degr...

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Autores principales: Omnus, Deike J., Pfirrmann, Thorsten, Andréasson, Claes, Ljungdahl, Per O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145550/
https://www.ncbi.nlm.nih.gov/pubmed/21653827
http://dx.doi.org/10.1091/mbc.E11-04-0282
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author Omnus, Deike J.
Pfirrmann, Thorsten
Andréasson, Claes
Ljungdahl, Per O.
author_facet Omnus, Deike J.
Pfirrmann, Thorsten
Andréasson, Claes
Ljungdahl, Per O.
author_sort Omnus, Deike J.
collection PubMed
description 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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spelling pubmed-31455502011-10-16 A phosphodegron controls nutrient-induced proteasomal activation of the signaling protease Ssy5 Omnus, Deike J. Pfirrmann, Thorsten Andréasson, Claes Ljungdahl, Per O. Mol Biol Cell Articles 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. The American Society for Cell Biology 2011-08-01 /pmc/articles/PMC3145550/ /pubmed/21653827 http://dx.doi.org/10.1091/mbc.E11-04-0282 Text en © 2011 Omnus et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Omnus, Deike J.
Pfirrmann, Thorsten
Andréasson, Claes
Ljungdahl, Per O.
A phosphodegron controls nutrient-induced proteasomal activation of the signaling protease Ssy5
title A phosphodegron controls nutrient-induced proteasomal activation of the signaling protease Ssy5
title_full A phosphodegron controls nutrient-induced proteasomal activation of the signaling protease Ssy5
title_fullStr A phosphodegron controls nutrient-induced proteasomal activation of the signaling protease Ssy5
title_full_unstemmed A phosphodegron controls nutrient-induced proteasomal activation of the signaling protease Ssy5
title_short A phosphodegron controls nutrient-induced proteasomal activation of the signaling protease Ssy5
title_sort phosphodegron controls nutrient-induced proteasomal activation of the signaling protease ssy5
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145550/
https://www.ncbi.nlm.nih.gov/pubmed/21653827
http://dx.doi.org/10.1091/mbc.E11-04-0282
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