ArticleMolecular & cellular proteomics : MCP2016
Methylthioadenosine (MTA) Regulates Liver Cells Proteome and Methylproteome: Implications in Liver Biology and Disease.
Article in Molecular & cellular proteomics : MCP, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Metabolomics Analysis Reveals Altered Metabolic Pathways and Response to Doxorubicin in Drug-Resistant Triple-Negative Breast Cancer Cells.Metabolites · 2023Article
- Review
- Reduced symmetric dimethylation stabilizes vimentin and promotes metastasis in MTAP-deficient lung cancer.EMBO reports · 2022Article
- Integration of themBio · 2022Article
- Excess S-adenosylmethionine inhibits methylation via catabolism to adenine.Communications biology · 2022Article
- Monitoring one-carbon metabolism by mass spectrometry to assess liver function and disease.Journal of physiology and biochemistry · 2022Article
- Epigenetic Regulation of Fanconi Anemia Genes Implicates PRMT5 Blockage as a Strategy for Tumor Chemosensitization.Molecular cancer research : MCR · 2021Article
- Untargeted metabolomic analysis of urine samples for diagnosis of inherited metabolic disorders.Functional & integrative genomics · 2021Article
- Solid phase microextraction chemical biopsy tool for monitoring of doxorubicin residue during in vivo lung chemo-perfusion.Journal of pharmaceutical analysis · 2021Article
- A Key Silencing Histone Mark on Chromatin Is Lost When Colorectal Adenocarcinoma Cells Are Depleted of Methionine by Methionine γ-Lyase.Frontiers in molecular biosciences · 2021Article
- MTAP Loss Promotes Stemness in Glioblastoma and Confers Unique Susceptibility to Purine Starvation.Cancer research · 2019Article
- 5'-Methylthioadenosine and Cancer: old molecules, new understanding.Journal of Cancer · 2019Review
- Metabolomic Profiling of Portal Blood and Bile Reveals Metabolic Signatures of Primary Sclerosing Cholangitis.International journal of molecular sciences · 2018Article
- Methylthioadenosine Suppresses Salmonella Virulence.Infection and immunity · 2018Article
- Systems Analyses Reveal Physiological Roles and Genetic Regulators of Liver Lipid Species.Cell systems · 2018Article
- Metabolic adaptation of short-living growth hormone transgenic mice to methionine restriction and supplementation.Annals of the New York Academy of Sciences · 2018Article
- Bioinformatics and Drug Discovery.Current topics in medicinal chemistry · 2017Review
- Highlights of the Biology and Disease-driven Human Proteome Project, 2015-2016.Journal of proteome research · 2016Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methylthioadenosine phosphorylase (MTAP), a key enzyme in the adenine and methionine salvage pathways, catalyzes the hydrolysis of methylthioadenosine (MTA), a compound suggested to affect pivotal cellular processes in part through the regulation of protein methylation. MTAP is expressed in a wide range of cell types and tissues, and its deletion is common to cancer cells and in liver injury. The aim of this study was to investigate the proteome and methyl proteome alterations triggered by MTAP deficiency in liver cells to define novel regulatory mechanisms that may explain the pathogenic processes of liver diseases. iTRAQ analysis resulted in the identification of 216 differential proteins (p < 0.05) that suggest deregulation of cellular pathways as those mediated by ERK or NFκB. R-methyl proteome analysis led to the identification of 74 differentially methylated proteins between SK-Hep1 and SK-Hep1+ cells, including 116 new methylation sites. Restoring normal MTA levels in SK-Hep1+ cells parallels the specific methylation of 56 proteins, including KRT8, TGF, and CTF8A, which provides a novel regulatory mechanism of their activity with potential implications in carcinogenesis. Inhibition of RNA-binding proteins methylation is especially relevant upon accumulation of MTA. As an example, methylation of quaking protein in Arg(242) and Arg(256) in SK-Hep1+ cells may play a pivotal role in the regulation of its activity as indicated by the up-regulation of its target protein p27(kip1) The phenotype associated with a MTAP deficiency was further verified in the liver of MTAP± mice. Our data support that MTAP deficiency leads to MTA accumulation and deregulation of central cellular pathways, increasing proliferation and decreasing the susceptibility to chemotherapeutic drugs, which involves differential protein methylation. Data are available via ProteomeXchange with identifier PXD002957 (http://www.ebi.ac.uk/pride/archive/projects/PXD002957).
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