Web of Science: 10 cites, Scopus: 10 cites, Google Scholar: cites,
Overexpression of budding yeast protein phosphatase Ppz1 impairs translation
Calafí, Carlos (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
López-Malo, María (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Velázquez, Diego (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Zhang, Chunyi (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Fernández-Fernández, José (Universidad de Sevilla. Departamento de Genética)
Rodríguez-Galán, Olga (Universidad de Sevilla. Departamento de Genética)
de la Cruz, Jesús (Universidad de Sevilla. Departamento de Genética)
Ariño Carmona, Joaquín (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Casamayor Gracia, Antonio (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular

Data: 2020
Resum: The Ser/Thr protein phosphatase Ppz1 from Saccharomyces cerevisiae is the best characterized member of a family of enzymes only found in fungi. Ppz1 is regulated in vivo by two inhibitory subunits, Hal3 and Vhs3, which are moonlighting proteins also involved in the decarboxylation of the 4-phosphopantothenoylcysteine (PPC) intermediate required for coenzyme A biosynthesis. It has been reported that, when overexpressed, Ppz1 is the most toxic protein in yeast. However, the reasons for such toxicity have not been elucidated. Here we show that the detrimental effect of excessive Ppz1 expression is due to an increase in its phosphatase activity and not to a plausible down-titration of the PPC decarboxylase components. We have identified several genes encoding ribosomal proteins and ribosome assembly factors as mild high-copy suppressors of the toxic Ppz1 effect. Ppz1 binds to ribosomes engaged in translation and copurifies with diverse ribosomal proteins and translation factors. Ppz1 overexpression results in Gcn2-dependent increased phosphorylation of eIF2α at Ser-51. Consistently, deletion of GCN2 partially suppresses the growth defect of a Ppz1 overexpressing strain. We propose that the deleterious effects of Ppz1 overexpression are in part due to alteration in normal protein synthesis.
Ajuts: Ministerio de Economía y Competitividad BFU2017-82574-P
Ministerio de Economía y Competitividad BFU2016-75352-P
Nota: This research was funded by grant BFU2017-82574-P to JA and AC, and BFU2016-75352-P to JdlC (AEI / FEDER, EU; Ministerio de Industria, Economía y Competitividad, Spain, and ERDF). CC and JF-F were recipient of a PhD fellowship from the Ministerio de Economía y Competitividad (Spain). CZ was recipient of a PhD fellowship from the China Scholarship Council. DV was recipient of a PhD fellowship from UAB.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió acceptada per publicar
Matèria: Ppz1 ; Protein phosphatase ; Ribosomal proteins ; Translation initiation ; Yeast
Publicat a: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1867, Issue 8 (August 2020) , art. 118727, ISSN 0167-4889

DOI: 10.1016/j.bbamcr.2020.118727
PMID: 32339526


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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Biotecnologia i de Biomedicina (IBB)
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 Registre creat el 2020-11-09, darrera modificació el 2022-04-04



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