Yeast Ppz1 protein phosphatase toxicity involves the alteration of multiple cellular targets
Control of the protein phosphorylation status is a major mechanism for regulation of cellular processes, and its alteration often lead to functional disorders. Ppz1, a protein phosphatase only found in fungi, is the most toxic protein when overexpressed in Saccharomyces cerevisiae . To investigate t...
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| Veröffentlicht in: | Scientific reports 2020-09, Vol.10 (1), p.15613, Article 15613 |
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| creator | Velázquez, Diego Albacar, Marcel Zhang, Chunyi Calafí, Carlos López-Malo, María Torres-Torronteras, Javier Martí, Ramón Kovalchuk, Sergey I. Pinson, Benoit Jensen, Ole N. Daignan-Fornier, Bertrand Casamayor, Antonio Ariño, Joaquín |
| description | Control of the protein phosphorylation status is a major mechanism for regulation of cellular processes, and its alteration often lead to functional disorders. Ppz1, a protein phosphatase only found in fungi, is the most toxic protein when overexpressed in
Saccharomyces cerevisiae
. To investigate the molecular basis of this phenomenon, we carried out combined genome-wide transcriptomic and phosphoproteomic analyses. We have found that Ppz1 overexpression causes major changes in gene expression, affecting ~ 20% of the genome, together with oxidative stress and increase in total adenylate pools. Concurrently, we observe changes in the phosphorylation pattern of near 400 proteins (mainly dephosphorylated), including many proteins involved in mitotic cell cycle and bud emergence, rapid dephosphorylation of Snf1 and its downstream transcription factor Mig1, and phosphorylation of Hog1 and its downstream transcription factor Sko1. Deletion of
HOG1
attenuates the growth defect of Ppz1-overexpressing cells, while that of
SKO1
aggravates it. Our results demonstrate that Ppz1 overexpression has a widespread impact in the yeast cells and reveals new aspects of the regulation of the cell cycle. |
| doi_str_mv | 10.1038/s41598-020-72391-y |
| format | Article |
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Saccharomyces cerevisiae
. To investigate the molecular basis of this phenomenon, we carried out combined genome-wide transcriptomic and phosphoproteomic analyses. We have found that Ppz1 overexpression causes major changes in gene expression, affecting ~ 20% of the genome, together with oxidative stress and increase in total adenylate pools. Concurrently, we observe changes in the phosphorylation pattern of near 400 proteins (mainly dephosphorylated), including many proteins involved in mitotic cell cycle and bud emergence, rapid dephosphorylation of Snf1 and its downstream transcription factor Mig1, and phosphorylation of Hog1 and its downstream transcription factor Sko1. Deletion of
HOG1
attenuates the growth defect of Ppz1-overexpressing cells, while that of
SKO1
aggravates it. Our results demonstrate that Ppz1 overexpression has a widespread impact in the yeast cells and reveals new aspects of the regulation of the cell cycle.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-72391-y</identifier><identifier>PMID: 32973189</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208 ; 631/326 ; 631/337 ; 631/45 ; Cell Cycle ; DNA Damage ; Gene Expression Regulation, Fungal ; Humanities and Social Sciences ; Life Sciences ; Metabolome ; multidisciplinary ; Phosphoprotein Phosphatases - genetics ; Phosphoprotein Phosphatases - metabolism ; Phosphorylation ; Reactive Oxygen Species ; Saccharomyces cerevisiae - genetics ; Saccharomyces cerevisiae - growth & development ; Saccharomyces cerevisiae - metabolism ; Saccharomyces cerevisiae Proteins - genetics ; Saccharomyces cerevisiae Proteins - metabolism ; Science ; Science (multidisciplinary) ; Transcriptome</subject><ispartof>Scientific reports, 2020-09, Vol.10 (1), p.15613, Article 15613</ispartof><rights>The Author(s) 2020</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c517t-514d94ff486ace7e7989346e2e23d72b0acb83eaeb63fc1f49250002ca85f26a3</citedby><cites>FETCH-LOGICAL-c517t-514d94ff486ace7e7989346e2e23d72b0acb83eaeb63fc1f49250002ca85f26a3</cites><orcidid>0000-0003-2936-9058 ; 0000-0003-2352-9700 ; 0000-0003-0324-605X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519054/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519054/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,27907,27908,41103,42172,51559,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32973189$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02992849$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Velázquez, Diego</creatorcontrib><creatorcontrib>Albacar, Marcel</creatorcontrib><creatorcontrib>Zhang, Chunyi</creatorcontrib><creatorcontrib>Calafí, Carlos</creatorcontrib><creatorcontrib>López-Malo, María</creatorcontrib><creatorcontrib>Torres-Torronteras, Javier</creatorcontrib><creatorcontrib>Martí, Ramón</creatorcontrib><creatorcontrib>Kovalchuk, Sergey I.</creatorcontrib><creatorcontrib>Pinson, Benoit</creatorcontrib><creatorcontrib>Jensen, Ole N.</creatorcontrib><creatorcontrib>Daignan-Fornier, Bertrand</creatorcontrib><creatorcontrib>Casamayor, Antonio</creatorcontrib><creatorcontrib>Ariño, Joaquín</creatorcontrib><title>Yeast Ppz1 protein phosphatase toxicity involves the alteration of multiple cellular targets</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Control of the protein phosphorylation status is a major mechanism for regulation of cellular processes, and its alteration often lead to functional disorders. Ppz1, a protein phosphatase only found in fungi, is the most toxic protein when overexpressed in
Saccharomyces cerevisiae
. To investigate the molecular basis of this phenomenon, we carried out combined genome-wide transcriptomic and phosphoproteomic analyses. We have found that Ppz1 overexpression causes major changes in gene expression, affecting ~ 20% of the genome, together with oxidative stress and increase in total adenylate pools. Concurrently, we observe changes in the phosphorylation pattern of near 400 proteins (mainly dephosphorylated), including many proteins involved in mitotic cell cycle and bud emergence, rapid dephosphorylation of Snf1 and its downstream transcription factor Mig1, and phosphorylation of Hog1 and its downstream transcription factor Sko1. Deletion of
HOG1
attenuates the growth defect of Ppz1-overexpressing cells, while that of
SKO1
aggravates it. Our results demonstrate that Ppz1 overexpression has a widespread impact in the yeast cells and reveals new aspects of the regulation of the cell cycle.</description><subject>631/208</subject><subject>631/326</subject><subject>631/337</subject><subject>631/45</subject><subject>Cell Cycle</subject><subject>DNA Damage</subject><subject>Gene Expression Regulation, Fungal</subject><subject>Humanities and Social Sciences</subject><subject>Life Sciences</subject><subject>Metabolome</subject><subject>multidisciplinary</subject><subject>Phosphoprotein Phosphatases - genetics</subject><subject>Phosphoprotein Phosphatases - metabolism</subject><subject>Phosphorylation</subject><subject>Reactive Oxygen Species</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Saccharomyces cerevisiae - growth & development</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Saccharomyces cerevisiae Proteins - genetics</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Transcriptome</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kcFrHCEUxiWkNCHNP9BD8NrDtPrUnfFSCCFpCgvtoT0EAuK6b3YM7jiou2T719d02pD20Hfx4ft-H08_Qt5y9p4z0X3IkivdNQxY04LQvDkckVNgUjUgAI5f9CfkPOcHVkuBlly_JicCdCt4p0_J_R3aXOjX6QenU4oF_UinIeZpsMVmpCU-eufLgfpxH8MeMy0DUhsKJlt8HGns6XYXip8CUoch7IJNtNi0wZLfkFe9DRnPf59n5PvN9ber22b55dPnq8tl4xRvS6O4XGvZ97JbWIcttrrTQi4QEMS6hRWzbtUJtLhaiN7xXmpQ9TXgbKd6WFhxRj7OvtNutcW1w7EkG8yU_Namg4nWm78nox_MJu5Nq7hmSlaDd7PB8A92e7k0T3cMtIZO6j2vWpi1LsWcE_bPAGfmKRozR1MZZn5FYw4Vuni54TPyJ4gqELMg19G4wWQe4i6N9df-Z_sTMd-c8g</recordid><startdate>20200924</startdate><enddate>20200924</enddate><creator>Velázquez, Diego</creator><creator>Albacar, Marcel</creator><creator>Zhang, Chunyi</creator><creator>Calafí, Carlos</creator><creator>López-Malo, María</creator><creator>Torres-Torronteras, Javier</creator><creator>Martí, Ramón</creator><creator>Kovalchuk, Sergey I.</creator><creator>Pinson, Benoit</creator><creator>Jensen, Ole N.</creator><creator>Daignan-Fornier, Bertrand</creator><creator>Casamayor, Antonio</creator><creator>Ariño, Joaquín</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2936-9058</orcidid><orcidid>https://orcid.org/0000-0003-2352-9700</orcidid><orcidid>https://orcid.org/0000-0003-0324-605X</orcidid></search><sort><creationdate>20200924</creationdate><title>Yeast Ppz1 protein phosphatase toxicity involves the alteration of multiple cellular targets</title><author>Velázquez, Diego ; Albacar, Marcel ; Zhang, Chunyi ; Calafí, Carlos ; López-Malo, María ; Torres-Torronteras, Javier ; Martí, Ramón ; Kovalchuk, Sergey I. ; Pinson, Benoit ; Jensen, Ole N. ; Daignan-Fornier, Bertrand ; Casamayor, Antonio ; Ariño, Joaquín</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c517t-514d94ff486ace7e7989346e2e23d72b0acb83eaeb63fc1f49250002ca85f26a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/208</topic><topic>631/326</topic><topic>631/337</topic><topic>631/45</topic><topic>Cell Cycle</topic><topic>DNA Damage</topic><topic>Gene Expression Regulation, Fungal</topic><topic>Humanities and Social Sciences</topic><topic>Life Sciences</topic><topic>Metabolome</topic><topic>multidisciplinary</topic><topic>Phosphoprotein Phosphatases - genetics</topic><topic>Phosphoprotein Phosphatases - metabolism</topic><topic>Phosphorylation</topic><topic>Reactive Oxygen Species</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Saccharomyces cerevisiae - growth & development</topic><topic>Saccharomyces cerevisiae - metabolism</topic><topic>Saccharomyces cerevisiae Proteins - genetics</topic><topic>Saccharomyces cerevisiae Proteins - metabolism</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Transcriptome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Velázquez, Diego</creatorcontrib><creatorcontrib>Albacar, Marcel</creatorcontrib><creatorcontrib>Zhang, Chunyi</creatorcontrib><creatorcontrib>Calafí, Carlos</creatorcontrib><creatorcontrib>López-Malo, María</creatorcontrib><creatorcontrib>Torres-Torronteras, Javier</creatorcontrib><creatorcontrib>Martí, Ramón</creatorcontrib><creatorcontrib>Kovalchuk, Sergey I.</creatorcontrib><creatorcontrib>Pinson, Benoit</creatorcontrib><creatorcontrib>Jensen, Ole N.</creatorcontrib><creatorcontrib>Daignan-Fornier, Bertrand</creatorcontrib><creatorcontrib>Casamayor, Antonio</creatorcontrib><creatorcontrib>Ariño, Joaquín</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Velázquez, Diego</au><au>Albacar, Marcel</au><au>Zhang, Chunyi</au><au>Calafí, Carlos</au><au>López-Malo, María</au><au>Torres-Torronteras, Javier</au><au>Martí, Ramón</au><au>Kovalchuk, Sergey I.</au><au>Pinson, Benoit</au><au>Jensen, Ole N.</au><au>Daignan-Fornier, Bertrand</au><au>Casamayor, Antonio</au><au>Ariño, Joaquín</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Yeast Ppz1 protein phosphatase toxicity involves the alteration of multiple cellular targets</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-09-24</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>15613</spage><pages>15613-</pages><artnum>15613</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Control of the protein phosphorylation status is a major mechanism for regulation of cellular processes, and its alteration often lead to functional disorders. Ppz1, a protein phosphatase only found in fungi, is the most toxic protein when overexpressed in
Saccharomyces cerevisiae
. To investigate the molecular basis of this phenomenon, we carried out combined genome-wide transcriptomic and phosphoproteomic analyses. We have found that Ppz1 overexpression causes major changes in gene expression, affecting ~ 20% of the genome, together with oxidative stress and increase in total adenylate pools. Concurrently, we observe changes in the phosphorylation pattern of near 400 proteins (mainly dephosphorylated), including many proteins involved in mitotic cell cycle and bud emergence, rapid dephosphorylation of Snf1 and its downstream transcription factor Mig1, and phosphorylation of Hog1 and its downstream transcription factor Sko1. Deletion of
HOG1
attenuates the growth defect of Ppz1-overexpressing cells, while that of
SKO1
aggravates it. Our results demonstrate that Ppz1 overexpression has a widespread impact in the yeast cells and reveals new aspects of the regulation of the cell cycle.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32973189</pmid><doi>10.1038/s41598-020-72391-y</doi><orcidid>https://orcid.org/0000-0003-2936-9058</orcidid><orcidid>https://orcid.org/0000-0003-2352-9700</orcidid><orcidid>https://orcid.org/0000-0003-0324-605X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/208 631/326 631/337 631/45 Cell Cycle DNA Damage Gene Expression Regulation, Fungal Humanities and Social Sciences Life Sciences Metabolome multidisciplinary Phosphoprotein Phosphatases - genetics Phosphoprotein Phosphatases - metabolism Phosphorylation Reactive Oxygen Species Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - growth & development Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - metabolism Science Science (multidisciplinary) Transcriptome |
| title | Yeast Ppz1 protein phosphatase toxicity involves the alteration of multiple cellular targets |
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