Article ID Journal Published Year Pages File Type
1225234 Journal of Proteomics 2012 14 Pages PDF
Abstract

Methionine adenosyltransferase I/III (MATI/III) synthesizes S-adenosylmethionine (SAM) in quiescent hepatocytes. Its activity is compromised in most liver diseases including liver cancer. Since SAM is a driver of hepatocytes fate we have studied the effect of re-expressing MAT1A in hepatoma Huh7 cells using proteomics. MAT1A expression leads to SAM levels close to those found in quiescent hepatocytes and induced apoptosis. Normalization of intracellular SAM induced alteration of 128 proteins identified by 2D-DIGE and gel-free methods, accounting for deregulation of central cellular functions including apoptosis, cell proliferation and survival. Human Dead-box protein 3 (DDX3X), a RNA helicase regulating RNA splicing, export, transcription and translation was down-regulated upon MAT1A expression. Our data support the regulation of DDX3X levels by SAM in a concentration and time dependent manner. Consistently, DDX3X arises as a primary target of SAM and a principal intermediate of its antitumoral effect. Based on the parallelism between SAM and DDX3X along the progression of liver disorders, and the results reported here, it is tempting to suggest that reduced SAM in the liver may lead to DDX3X up-regulation contributing to the pathogenic process and that replenishment of SAM might prove to have beneficial effects, at least in part by reducing DDX3X levels. This article is part of a Special Issue entitled: Proteomics: The clinical link.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (101 K)Download as PowerPoint slideHighlights► Expression of MAT1A in Huh7 cells leads to SAM levels close to quiescent hepatocytes. ► 128 differential proteins reveal alteration of essential pathways for cancer cells. ► SAM regulates DDX3X in a time and dose dependent manner. ► DDX3X mediates the antitumoral effect of SAM in hepatoma cells.

Related Topics
Physical Sciences and Engineering Chemistry Analytical Chemistry
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