Gcn5p and Ubp8p Affect Protein Ubiquitylation and Cell Proliferation by Altering the Fermentative/Respiratory Flux Balance in <italic toggle="yes">Saccharomyces cerevisiae</italic>

ABSTRACT Protein ubiquitylation regulates not only endocellular trafficking and proteasomal degradation but also the catalytic activity of enzymes. In Saccharomyces cerevisiae, we analyzed the composition of the ubiquitylated proteomes in strains lacking acetyltransferase Gcn5p, Ub-protease Ubp8p, o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Antonella De Palma, Giulia Fanelli, Elisabetta Cretella, Veronica De Luca, Raffaele Antonio Palladino, Valentina Panzeri, Valentina Roffia, Michele Saliola, Pierluigi Mauri, Patrizia Filetici
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	ubiquitylation Gcn5p Ubp8p glycolytic flux sugar utilization Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bd81e473ee064372a1520e4593a9d3b9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:bd81e473ee064372a1520e4593a9d3b9
record_format	dspace
spelling	oai:doaj.org-article:bd81e473ee064372a1520e4593a9d3b92021-11-15T15:56:44ZGcn5p and Ubp8p Affect Protein Ubiquitylation and Cell Proliferation by Altering the Fermentative/Respiratory Flux Balance in <italic toggle="yes">Saccharomyces cerevisiae</italic>10.1128/mBio.01504-202150-7511https://doaj.org/article/bd81e473ee064372a1520e4593a9d3b92020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01504-20https://doaj.org/toc/2150-7511ABSTRACT Protein ubiquitylation regulates not only endocellular trafficking and proteasomal degradation but also the catalytic activity of enzymes. In Saccharomyces cerevisiae, we analyzed the composition of the ubiquitylated proteomes in strains lacking acetyltransferase Gcn5p, Ub-protease Ubp8p, or both to understand their involvement in the regulation of protein ubiquitylation. We analyzed His6Ub proteins with a proteomic approach coupling micro-liquid chromatography and tandem mass spectrometry (μLC-MS/MS) in gcn5Δ, ubp8Δ and ubp8Δ gcn5Δ strains. The Ub-proteome altered in the absence of Gcn5p, Ubp8p, or both was characterized, showing that 43% of the proteins was shared in all strains, suggesting their functional relationship. Remarkably, all major glycolytic enzymes showed increased ubiquitylation. Phosphofructokinase 1, the key enzyme of glycolytic flux, showed a higher and altered pattern of ubiquitylation in gcn5Δ and ubp8Δ strains. Severe defects of growth in poor sugar and altered glucose consumption confirmed a direct role of Gcn5p and Ubp8p in affecting the REDOX balance of the cell. IMPORTANCE We propose a study showing a novel role of Gcn5p and Ubp8p in the process of ubiquitylation of the yeast proteome which includes main glycolytic enzymes. Interestingly, in the absence of Gcn5p and Ubp8p glucose consumption and redox balance were altered in yeast. We believe that these results and the role of Gcn5p and Ubp8p in sugar metabolism might open new perspectives of research leading to novel protocols for counteracting the enhanced glycolysis in tumors.Antonella De PalmaGiulia FanelliElisabetta CretellaVeronica De LucaRaffaele Antonio PalladinoValentina PanzeriValentina RoffiaMichele SaliolaPierluigi MauriPatrizia FileticiAmerican Society for MicrobiologyarticleubiquitylationGcn5pUbp8pglycolytic fluxsugar utilizationMicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	ubiquitylation Gcn5p Ubp8p glycolytic flux sugar utilization Microbiology QR1-502
spellingShingle	ubiquitylation Gcn5p Ubp8p glycolytic flux sugar utilization Microbiology QR1-502 Antonella De Palma Giulia Fanelli Elisabetta Cretella Veronica De Luca Raffaele Antonio Palladino Valentina Panzeri Valentina Roffia Michele Saliola Pierluigi Mauri Patrizia Filetici Gcn5p and Ubp8p Affect Protein Ubiquitylation and Cell Proliferation by Altering the Fermentative/Respiratory Flux Balance in <italic toggle="yes">Saccharomyces cerevisiae</italic>
description	ABSTRACT Protein ubiquitylation regulates not only endocellular trafficking and proteasomal degradation but also the catalytic activity of enzymes. In Saccharomyces cerevisiae, we analyzed the composition of the ubiquitylated proteomes in strains lacking acetyltransferase Gcn5p, Ub-protease Ubp8p, or both to understand their involvement in the regulation of protein ubiquitylation. We analyzed His6Ub proteins with a proteomic approach coupling micro-liquid chromatography and tandem mass spectrometry (μLC-MS/MS) in gcn5Δ, ubp8Δ and ubp8Δ gcn5Δ strains. The Ub-proteome altered in the absence of Gcn5p, Ubp8p, or both was characterized, showing that 43% of the proteins was shared in all strains, suggesting their functional relationship. Remarkably, all major glycolytic enzymes showed increased ubiquitylation. Phosphofructokinase 1, the key enzyme of glycolytic flux, showed a higher and altered pattern of ubiquitylation in gcn5Δ and ubp8Δ strains. Severe defects of growth in poor sugar and altered glucose consumption confirmed a direct role of Gcn5p and Ubp8p in affecting the REDOX balance of the cell. IMPORTANCE We propose a study showing a novel role of Gcn5p and Ubp8p in the process of ubiquitylation of the yeast proteome which includes main glycolytic enzymes. Interestingly, in the absence of Gcn5p and Ubp8p glucose consumption and redox balance were altered in yeast. We believe that these results and the role of Gcn5p and Ubp8p in sugar metabolism might open new perspectives of research leading to novel protocols for counteracting the enhanced glycolysis in tumors.
format	article
author	Antonella De Palma Giulia Fanelli Elisabetta Cretella Veronica De Luca Raffaele Antonio Palladino Valentina Panzeri Valentina Roffia Michele Saliola Pierluigi Mauri Patrizia Filetici
author_facet	Antonella De Palma Giulia Fanelli Elisabetta Cretella Veronica De Luca Raffaele Antonio Palladino Valentina Panzeri Valentina Roffia Michele Saliola Pierluigi Mauri Patrizia Filetici
author_sort	Antonella De Palma
title	Gcn5p and Ubp8p Affect Protein Ubiquitylation and Cell Proliferation by Altering the Fermentative/Respiratory Flux Balance in <italic toggle="yes">Saccharomyces cerevisiae</italic>
title_short	Gcn5p and Ubp8p Affect Protein Ubiquitylation and Cell Proliferation by Altering the Fermentative/Respiratory Flux Balance in <italic toggle="yes">Saccharomyces cerevisiae</italic>
title_full	Gcn5p and Ubp8p Affect Protein Ubiquitylation and Cell Proliferation by Altering the Fermentative/Respiratory Flux Balance in <italic toggle="yes">Saccharomyces cerevisiae</italic>
title_fullStr	Gcn5p and Ubp8p Affect Protein Ubiquitylation and Cell Proliferation by Altering the Fermentative/Respiratory Flux Balance in <italic toggle="yes">Saccharomyces cerevisiae</italic>
title_full_unstemmed	Gcn5p and Ubp8p Affect Protein Ubiquitylation and Cell Proliferation by Altering the Fermentative/Respiratory Flux Balance in <italic toggle="yes">Saccharomyces cerevisiae</italic>
title_sort	gcn5p and ubp8p affect protein ubiquitylation and cell proliferation by altering the fermentative/respiratory flux balance in <italic toggle="yes">saccharomyces cerevisiae</italic>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/bd81e473ee064372a1520e4593a9d3b9
work_keys_str_mv	AT antonelladepalma gcn5pandubp8paffectproteinubiquitylationandcellproliferationbyalteringthefermentativerespiratoryfluxbalanceinitalictoggleyessaccharomycescerevisiaeitalic AT giuliafanelli gcn5pandubp8paffectproteinubiquitylationandcellproliferationbyalteringthefermentativerespiratoryfluxbalanceinitalictoggleyessaccharomycescerevisiaeitalic AT elisabettacretella gcn5pandubp8paffectproteinubiquitylationandcellproliferationbyalteringthefermentativerespiratoryfluxbalanceinitalictoggleyessaccharomycescerevisiaeitalic AT veronicadeluca gcn5pandubp8paffectproteinubiquitylationandcellproliferationbyalteringthefermentativerespiratoryfluxbalanceinitalictoggleyessaccharomycescerevisiaeitalic AT raffaeleantoniopalladino gcn5pandubp8paffectproteinubiquitylationandcellproliferationbyalteringthefermentativerespiratoryfluxbalanceinitalictoggleyessaccharomycescerevisiaeitalic AT valentinapanzeri gcn5pandubp8paffectproteinubiquitylationandcellproliferationbyalteringthefermentativerespiratoryfluxbalanceinitalictoggleyessaccharomycescerevisiaeitalic AT valentinaroffia gcn5pandubp8paffectproteinubiquitylationandcellproliferationbyalteringthefermentativerespiratoryfluxbalanceinitalictoggleyessaccharomycescerevisiaeitalic AT michelesaliola gcn5pandubp8paffectproteinubiquitylationandcellproliferationbyalteringthefermentativerespiratoryfluxbalanceinitalictoggleyessaccharomycescerevisiaeitalic AT pierluigimauri gcn5pandubp8paffectproteinubiquitylationandcellproliferationbyalteringthefermentativerespiratoryfluxbalanceinitalictoggleyessaccharomycescerevisiaeitalic AT patriziafiletici gcn5pandubp8paffectproteinubiquitylationandcellproliferationbyalteringthefermentativerespiratoryfluxbalanceinitalictoggleyessaccharomycescerevisiaeitalic
_version_	1718427116380356608

Gcn5p and Ubp8p Affect Protein Ubiquitylation and Cell Proliferation by Altering the Fermentative/Respiratory Flux Balance in <italic toggle="yes">Saccharomyces cerevisiae</italic>

Ejemplares similares