ArticleOncotarget2015
Methionine adenosyltransferase α2 sumoylation positively regulate Bcl-2 expression in human colon and liver cancer cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- SUMOylation machinery protein, PIAS4 role in breast cancer cell proliferation and drug sensitivity.Molecular biology reports · 2026Article
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- A novel role of secreted methionine adenosyltransferase α2 in colorectal liver metastases.Journal of experimental & clinical cancer research : CR · 2025Article
- Posttranslational Regulation of Mammalian Sulfur Amino Acid Metabolism.International journal of molecular sciences · 2025Review
- Review
- The role of forkhead box M1-methionine adenosyltransferase 2 A/2B axis in liver inflammation and fibrosis.Nature communications · 2024Article
- Sumoylation of methionine adenosyltransferase alpha 1 promotes mitochondrial dysfunction in alcohol-associated liver disease.Hepatology (Baltimore, Md.) · 2024Article
- Article
- Role of non-canonical post-translational modifications in gastrointestinal tumors.Cancer cell international · 2023Review
- SUMOylation mediates the disassembly of the Smad4 nuclear export complex via RanGAP1 in KELOIDS.Journal of cellular and molecular medicine · 2023Article
- mTORC1-c-Myc pathway rewires methionine metabolism for HCC progression through suppressing SIRT4 mediated ADP ribosylation of MAT2A.Cell & bioscience · 2022Article
- Transcriptional signatures of the BCL2 family for individualized acute myeloid leukaemia treatment.Genome medicine · 2022Article
- Inhibition of MAT2A-Related Methionine Metabolism Enhances The Efficacy of Cisplatin on Cisplatin-Resistant Cells in Lung Cancer.Cell journal · 2022Article
- Review
- Methionine adenosyltransferases in liver cancer.World journal of gastroenterology · 2019Review
- Alterations of Methionine Metabolism as Potential Targets for the Prevention and Therapy of Hepatocellular Carcinoma.Medicina (Kaunas, Lithuania) · 2019Review
- UBA2 promotes proliferation of colorectal cancer.Molecular medicine reports · 2018Article
- Mechanisms of MAFG Dysregulation in Cholestatic Liver Injury and Development of Liver Cancer.Gastroenterology · 2018Article
- SUMOylation regulates cytochrome P450 2E1 expression and activity in alcoholic liver disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Neurotensin receptor type 2 protects B-cell chronic lymphocytic leukemia cells from apoptosis.Oncogene · 2018Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Ubiquitin-conjugating enzyme 9 (Ubc9) is required for sumoylation and inhibits apoptosis via Bcl-2 by unknown mechanism. Methionine adenosyltransferase 2A (MAT2A) encodes for MATα2, the catalytic subunit of the MATII isoenzyme that synthesizes S-adenosylmethionine (SAMe). Ubc9, Bcl-2 and MAT2A expression are up-regulated in several malignancies. Exogenous SAMe decreases Ubc9 and MAT2A expression and is pro-apoptotic in liver and colon cancer cells. Here we investigated whether there is interplay between Ubc9, MAT2A and Bcl-2. We used human colon and liver cancer cell lines RKO and HepG2, respectively, and confirmed key finding in colon cancer specimens. We found MATα2 can regulate Bcl-2 expression at multiple levels. MATα2 binds to Bcl-2 promoter to activate its transcription. This effect is independent of SAMe as MATα2 catalytic mutant was also effective. MATα2 also directly interacts with Bcl-2 to enhance its protein stability. MATα2's effect on Bcl-2 requires Ubc9 as MATα2's stability is influenced by sumoylation at K340, K372 and K394. Overexpressing wild type (but not less stable MATα2 sumoylation mutants) protected from 5-fluorouracil-induced apoptosis in both colon and liver cancer cells. Colon cancer have higher levels of sumoylated MATα2, total MATα2, Ubc9 and Bcl-2 and higher MATα2 binding to the Bcl-2 P2 promoter. Taken together, Ubc9's protective effect on apoptosis may be mediated at least in part by sumoylating and stabilizing MATα2 protein, which in turn positively maintains Bcl-2 expression. These interactions feed forward to further enhance growth and survival of the cancer cell.
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