Ask about this productRelated genes to: MAT2A antibody
- Gene:
- MAT2A NIH gene
- Name:
- methionine adenosyltransferase 2A
- Previous symbol:
- -
- Synonyms:
- SAMS2, MATA2, MATII
- Chromosome:
- 2p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1997-07-01
- Date modifiied:
- 2016-01-27
Related products to: MAT2A antibody
Related articles to: MAT2A antibody
- Central metabolites function as essential co-substrates for chromatin-modifying enzymes, directly linking cellular metabolism to chromatin regulation. Accordingly, whole-cell fluctuations in co-substrate availabilities have been shown to promote diverse phenotypes through chromatin-dependent mechanisms. There is emerging evidence that metabolic enzymes producing co-substrates for chromatin modifying enzymes can exist in the nucleus, suggesting that nucleus-specific metabolite availability regulates chromatin state. Here, we developed CRISPRm (CRISPR metabolite) to assess how nucleus-specific metabolic perturbations influence chromatin function. Five dCas9-metabolic enzyme fusions ( ., dCas9-ACSS2, -NMNAT1, -MAT2A, -GDH, and -AHCY) were used to modulate nuclear levels of essential co-substrates involved in histone (de)acetylation and (de)methylation reactions. Transient expression of all dCas9 fusions in HEK293T cells induced distinct global changes in gene expression patterns, with dCas9-ACSS2 (acetyl-CoA producing) and NMNAT1 (NAD producing) eliciting large opposing changes in gene expression, suggesting transcriptional responses to nuclear acetyl-CoA and NAD production may be directly facilitated by acetylation or deacetylation reactions, respectively. Targeting dCas9-ACSS2 and -NMNAT1 to promoters of select candidate genes revealed enhanced transcriptional modulation. dCas9-ACSS2 upregulated, and dCas9-NMNAT1 downregulated genes showed basal enrichment of H3K9ac, H3K18ac, H3K27ac, H3K4me3, and p300, suggesting these genomic loci reside within epigenetic environments susceptible to fluctuations in acetyl-CoA and NAD availability. Of significant genes altered, dCas9-MAT2A (SAM producing) increased expression of 72% whereas dCAS9-GDH (alpha-ketoglutarate producing) decreased expression of 79%. Surprisingly, dCAS9-AHCY (SAH hydrolysis) led to down-regulation of shared genes up-regulated by dCas9-MAT2A. The observations amongst the methylation-specific enzymes revealed unexpected and unique gene-regulatory sensitivities to SAM, SAH and alpha-ketoglutarate. Together, these results demonstrate the utility of CRISPRm in studying nuclear metabolic regulation of transcription and provide strong evidence that perturbations in nuclear co-substrates do not lead to a large mass- action changes in chromatin acetylation/methylation but rather to modulation of select chromatin-modifying enzymes with targeted transcription responses. - Source: PubMed
Publication date: 2026/05/10
Biesbrock Kellen VHaws Spencer ACormaty HarshiniSridharan RupaDenu John M - Methylthioadenosine phosphorylase () genomic loss is an emerging biomarker for PRMT5 and MAT2A inhibitors based on synthetic lethality. The gene is located on chromosome 9p21.3 near homozygous loss across tumor types, specific exons lost, expression, and the landscape of coalterations were assessed. - Source: PubMed
Publication date: 2026/05/14
Pavlick Dean CRengarajan ShruthiLee Jessica KJin Deter XFrampton Garrett MFendler Bernard JSavol AndrejGjoerup OleTukachinsky HannaHuang Richard S PSchrock Alexa BRoss Jeffrey SNecchi Andrea - Hepatic stellate cell (HSC) activation is a key driver of extracellular matrix (ECM) accumulation and liver fibrosis. Autophagy plays an essential role in regulating HSC activation, yet its metabolic regulation remains largely undefined. Curcumol, a bioactive compound derived from Curcuma longa, possesses potent antifibrotic activity, but the underlying metabolic mechanisms are unclear. In this study, we found that curcumol suppressed HSC activation and induced autophagy-dependent cell death, together with inhibition of methionine metabolism. Curcumol treatment reduced LX-2 cell viability and downregulated profibrogenic markers α-smooth muscle actin (α-SMA) and collagen type I (COL1A1) in a dose-dependent manner. Mechanistically, curcumol enhanced LC3-II accumulation, diminished p62 levels, and promoted autophagic vacuole formation, effects that were reversed by the autophagy inhibitor 3-methyladenine (3-MA). Silencing of ATG7 attenuated curcumol-induced autophagy-associated changes and cell death, supporting the involvement of ATG7 in this process. Furthermore, curcumol significantly reduced the expression of key methionine cycle enzymes MAT2A and AHCY. Supplementation with S-adenosylmethionine (SAM) partially reversed curcumol-associated changes in methionine metabolism and autophagy-related markers, and improved HSC viability, supporting a functional link between methionine metabolism and the observed phenotype. Collectively, these findings suggest that curcumol promotes autophagy-dependent death of HSCs in association with disrupted methionine metabolism, providing new insight into the metabolic basis of its antifibrotic action. - Source: PubMed
Publication date: 2026/05/08
Gao Yi-JieZhou YaLi Yi-NingYang Kai-YaoXia Si-WeiHu Meng-RuLi YangChen LiWang Fei-XiaLu ShuaiLian Na-QiZheng Shi-ZhongZhang Feng - Cancer progression is closely associated with metabolic reprogramming and immune evasion. Extracellular adenosine (eADO) metabolism regulates adenosine receptor activation within the tumor microenvironment (TME). Predominantly through the adenosine A2A receptor, and, in some contexts through the adenosine A2B receptor, eADO signaling suppresses antitumor immune responses and contributes to resistance to immunotherapy. Production of eADO is largely driven by ecto-5'-nucleotidase (CD73), which catalyzes the conversion of eADO monophosphate (AMP) into eADO. In parallel, methylthioadenosine phosphorylase (MTAP) deletion - frequently co-occurring with loss of cyclin-dependent kinase inhibitor 2A (CDKN2A) - does not increase eADO levels but, instead, leads to intracellular accumulation of methylthioadenosine (MTA), reshaping methylation homeostasis and creating selective metabolic dependencies involving protein arginine methyltransferase 5 (PRMT5) and methionine adenosyltransferase 2A (MAT2A). Recent evidence further indicates that nucleoside transport dynamics, particularly via equilibrative nucleoside transporter 1 (ENT1), regulate intracellular adenosine (iADO) availability in T cells, and represent an additional regulatory layer, linking extracellular purinergic signaling with intracellular immunometabolic control. Accordingly, we propose a functional immunometabolic convergence framework in which CD73-dependent extracellular eADO signaling, ENT1-regulated iADO handling, and MTAP loss-associated metabolic rewiring function as parallel yet cooperative processes that stabilize tumor immune escape. - Source: PubMed
Publication date: 2026/05/02
Pedone da Rosa VandrielFontana MichelliRichter Schmitz Carine RaquelBuzatto Maike ValentimGiacomelli Iuri RaielRoman Junior Walter AntônioBoison DetlevBagatini Margarete DulceFranco Vieira de Oliveira Maciel Sarah - Methionine addiction is a fundamental and general hallmark of cancer cells. Recombinant (rMETase) degrades extracellular methionine. rMETase, or other means of restricting methionine, in combination with numerous types of chemotherapy have shown synergistic cancer-selective efficacy. AG-270, a methionine adenosyltransferase 2A (MAT2A) inhibitor, blocks intracellular conversion of methionine to S-adenosylmethionine (SAM), the central reaction of the methionine cycle. The present study aimed to evaluate the synergistic and cancer-selective efficacy of the combination of AG-270 and rMETase in a co-culture model of cancer and normal cells. - Source: PubMed
Publication date: 2026/05/01
Kim JinsooHan QinghongLi ShukuanKang Byung MoMizuta KoheiAsano YoheiMiyashi YutaBouvet MichaelHoffman Robert M