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The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases

Methionine adenosyltransferases MAT I and MAT III (encoded by Mat1a) catalyze S-adenosylmethionine synthesis in normal liver. Major hepatic diseases concur with reduced levels of this essential methyl donor, which are primarily due to an expression switch from Mat1a towards Mat2a. Additional changes...

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Autores principales: Pérez, Claudia, Pérez-Zúñiga, Francisco J., Garrido, Francisco, Reytor, Edel, Portillo, Francisco, Pajares, María A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993455/
https://www.ncbi.nlm.nih.gov/pubmed/27548429
http://dx.doi.org/10.1371/journal.pone.0161672
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author Pérez, Claudia
Pérez-Zúñiga, Francisco J.
Garrido, Francisco
Reytor, Edel
Portillo, Francisco
Pajares, María A.
author_facet Pérez, Claudia
Pérez-Zúñiga, Francisco J.
Garrido, Francisco
Reytor, Edel
Portillo, Francisco
Pajares, María A.
author_sort Pérez, Claudia
collection PubMed
description Methionine adenosyltransferases MAT I and MAT III (encoded by Mat1a) catalyze S-adenosylmethionine synthesis in normal liver. Major hepatic diseases concur with reduced levels of this essential methyl donor, which are primarily due to an expression switch from Mat1a towards Mat2a. Additional changes in the association state and even in subcellular localization of these isoenzymes are also detected. All these alterations result in a reduced content of the moderate (MAT I) and high V(max) (MAT III) isoenzymes, whereas the low V(max) (MAT II) isoenzyme increases and nuclear accumulation of MAT I is observed. These changes derive in a reduced availability of cytoplasmic S-adenosylmethionine, together with an effort to meet its needs in the nucleus of damaged cells, rendering enhanced levels of certain epigenetic modifications. In this context, the putative role of protein-protein interactions in the control of S-adenosylmethionine synthesis has been scarcely studied. Using yeast two hybrid and a rat liver library we identified PDRG1 as an interaction target for MATα1 (catalytic subunit of MAT I and MAT III), further confirmation being obtained by immunoprecipitation and pull-down assays. Nuclear MATα interacts physically and functionally with the PDRG1 oncogene, resulting in reduced DNA methylation levels. Increased Pdrg1 expression is detected in acute liver injury and hepatoma cells, together with decreased Mat1a expression and nuclear accumulation of MATα1. Silencing of Pdrg1 expression in hepatoma cells alters their steady-state expression profile on microarrays, downregulating genes associated with tumor progression according to GO pathway analysis. Altogether, the results unveil the role of PDRG1 in the control of the nuclear methylation status through methionine adenosyltransferase binding and its putative collaboration in the progression of hepatic diseases.
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spelling pubmed-49934552016-09-12 The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases Pérez, Claudia Pérez-Zúñiga, Francisco J. Garrido, Francisco Reytor, Edel Portillo, Francisco Pajares, María A. PLoS One Research Article Methionine adenosyltransferases MAT I and MAT III (encoded by Mat1a) catalyze S-adenosylmethionine synthesis in normal liver. Major hepatic diseases concur with reduced levels of this essential methyl donor, which are primarily due to an expression switch from Mat1a towards Mat2a. Additional changes in the association state and even in subcellular localization of these isoenzymes are also detected. All these alterations result in a reduced content of the moderate (MAT I) and high V(max) (MAT III) isoenzymes, whereas the low V(max) (MAT II) isoenzyme increases and nuclear accumulation of MAT I is observed. These changes derive in a reduced availability of cytoplasmic S-adenosylmethionine, together with an effort to meet its needs in the nucleus of damaged cells, rendering enhanced levels of certain epigenetic modifications. In this context, the putative role of protein-protein interactions in the control of S-adenosylmethionine synthesis has been scarcely studied. Using yeast two hybrid and a rat liver library we identified PDRG1 as an interaction target for MATα1 (catalytic subunit of MAT I and MAT III), further confirmation being obtained by immunoprecipitation and pull-down assays. Nuclear MATα interacts physically and functionally with the PDRG1 oncogene, resulting in reduced DNA methylation levels. Increased Pdrg1 expression is detected in acute liver injury and hepatoma cells, together with decreased Mat1a expression and nuclear accumulation of MATα1. Silencing of Pdrg1 expression in hepatoma cells alters their steady-state expression profile on microarrays, downregulating genes associated with tumor progression according to GO pathway analysis. Altogether, the results unveil the role of PDRG1 in the control of the nuclear methylation status through methionine adenosyltransferase binding and its putative collaboration in the progression of hepatic diseases. Public Library of Science 2016-08-22 /pmc/articles/PMC4993455/ /pubmed/27548429 http://dx.doi.org/10.1371/journal.pone.0161672 Text en © 2016 Pérez et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pérez, Claudia
Pérez-Zúñiga, Francisco J.
Garrido, Francisco
Reytor, Edel
Portillo, Francisco
Pajares, María A.
The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases
title The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases
title_full The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases
title_fullStr The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases
title_full_unstemmed The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases
title_short The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases
title_sort oncogene pdrg1 is an interaction target of methionine adenosyltransferases
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993455/
https://www.ncbi.nlm.nih.gov/pubmed/27548429
http://dx.doi.org/10.1371/journal.pone.0161672
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