PXD002957 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Methyltioadenosine regulates liver cells proteome and methylproteome. Implications in liver biology and disease. |
Description | 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 lead 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 R242 and R256 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. |
HostingRepository | PRIDE |
AnnounceDate | 2016-02-01 |
AnnouncementXML | Submission_2016-02-01_11:33:18.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Emilie Bigaud |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue; monomethylated residue |
Instrument | TripleTOF 5600 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2015-09-22 01:41:51 | ID requested | |
⏵ 1 | 2016-02-01 11:33:19 | announced | |
Publication List
Bigaud E, Corrales FJ, Methylthioadenosine (MTA) Regulates Liver Cells Proteome and Methylproteome: Implications in Liver Biology and Disease. Mol Cell Proteomics, 15(5):1498-510(2016) [pubmed] |
Keyword List
ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project |
curator keyword: Biomedical |
submitter keyword: Human, liver, MTA, methylation, MSMS |
Contact List
Fernando J Corrales |
contact affiliation | Department of Hepatology, Proteomics laboratory. CIMA, University of Navarra. 31008 Pamplona, Spain. |
contact email | fjcorrales@unav.es |
lab head | |
Emilie Bigaud |
contact affiliation | Center for applied medical research (CIMA), University of Navarra |
contact email | emilie.bigaud@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD002957
- Label: PRIDE project
- Name: Methyltioadenosine regulates liver cells proteome and methylproteome. Implications in liver biology and disease.