2015dcb0de06e23ef08d6606e01a83d8 ijmolsci_a2022v23n8p4304.pdf cc7285a1bdce6601fad08a377c9f19d9cfc4239c ijmolsci_a2022v23n8p4304.pdf 132421f76d976eb03994c5106bafd42ad0e577e692941b7348d8d7d802d6dabe ijmolsci_a2022v23n8p4304.pdf Title: When Phosphatases Go Mad: The Molecular Basis for Toxicity of Yeast Ppz1 Subject: The fact that overexpression of the yeast Ser/Thr protein phosphatase Ppz1 induces a dramatic halt in cell proliferation was known long ago, but only work in the last few years has provided insight into the molecular basis for this toxicity. Overexpression of Ppz1 causes abundant changes in gene expression and modifies the phosphorylation state of more than 150 proteins, including key signaling protein kinases such as Hog1 or Snf1. Diverse cellular processes are altered: halt in translation, failure to properly adapt to low glucose supply, acidification of the cytosol, or depletion of intracellular potassium content are a few examples. Therefore, the toxicity derived from an excess of Ppz1 appears to be multifactorial, the characteristic cell growth blockage thus arising from the combination of various altered processes. Notably, overexpression of the Ppz1 regulatory subunit Hal3 fully counteracts the toxic effects of the phosphatase, and this process involves intracellular relocation of the phosphatase to internal membranes. Keywords: protein phosphatases; protein overexpression; transcriptomics; phosphoproteomics; intracellular signaling; pH homeostasis; Saccharomyces cerevisiae Author: Antonio Casamayor and Joaquín Ariño Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Apr 14 09:48:14 2022 CEST ModDate: Thu Apr 14 09:54:39 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1125712 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 DRYAID+VnURWPalladioL Type 1 Custom yes yes no 15 0 KCCOPO+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 ULANXP+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 YZBBXS+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 44 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 56 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 59 0 ZNTIVN+URWPalladioL-BoldItal Type 1 Custom yes yes no 84 0 QDCWHF+EURM10 Type 1 Builtin yes yes no 88 0 UISLOM+TeX-tipa9 Type 1 Builtin yes yes no 95 0 SOSCBV+CMSY10 Type 1 Builtin yes yes no 99 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-07-07 02:25:37 CEST RepresentationInformation: ijmolsci_a2022v23n8p4304.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-04-20 11:44:13 CEST Size: 1125712 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 436 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4923ab24 Item: Title: The N-Terminal Extension of Ppz1 Is an Important Factor for Toxicity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: PPZ1 Overexpression Affects Protein Synthesis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: An Excess of Ppz1 Interferes with Normal Adaptation to Low Glucose Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Ppz1 Overexpression Affects Diverse Signaling Pathways Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: The Alteration of Monovalent Cation and pH Homeostasis Contributes to Ppz1 Toxicity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Hal3: Just an Inhibitor of Ppz1 Activity? Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Info: Title: When Phosphatases Go Mad: The Molecular Basis for Toxicity of Yeast Ppz1 Author: Antonio Casamayor and Joaquín Ariño Subject: The fact that overexpression of the yeast Ser/Thr protein phosphatase Ppz1 induces a dramatic halt in cell proliferation was known long ago, but only work in the last few years has provided insight into the molecular basis for this toxicity. Overexpression of Ppz1 causes abundant changes in gene expression and modifies the phosphorylation state of more than 150 proteins, including key signaling protein kinases such as Hog1 or Snf1. Diverse cellular processes are altered: halt in translation, failure to properly adapt to low glucose supply, acidification of the cytosol, or depletion of intracellular potassium content are a few examples. Therefore, the toxicity derived from an excess of Ppz1 appears to be multifactorial, the characteristic cell growth blockage thus arising from the combination of various altered processes. Notably, overexpression of the Ppz1 regulatory subunit Hal3 fully counteracts the toxic effects of the phosphatase, and this process involves intracellular relocation of the phosphatase to internal membranes. 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