Ask about this productRelated genes to: SHMT2 Blocking Peptide
- Gene:
- SHMT2 NIH gene
- Name:
- serine hydroxymethyltransferase 2
- Previous symbol:
- SHMT
- Synonyms:
- -
- Chromosome:
- 12q12-q14
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2016-03-11
Related products to: SHMT2 Blocking Peptide
Related articles to: SHMT2 Blocking Peptide
- Activation of YAP during the acute phase of pressure overload induces compensatory cardiac hypertrophy by activating aerobic glycolysis. One potential mechanism mediating the salutary action of YAP is an accumulation of serine, which provides building blocks essential for the growth and survival of cardiomyocytes. We investigated the molecular mechanism through which YAP promotes serine accumulation in the heart during the acute phase of pressure overload. Overexpression of YAP upregulated PHGDH, PSAT1, PSPH, components of the serine synthesis pathway (SSP), and SHMT1, but not SHMT2, an enzyme involved in interconversion between serine and glycine, in cardiomyocytes at both the mRNA and protein levels. Upregulation of these enzymes during transverse aortic constriction (TAC) was abolished in cardiac specific Yap knockout (Yap-chKO) mice. Downregulation of Phgdh attenuated YAP-induced increases in SSP metabolites, including phospho-serine, serine, glycine and S-adenosylmethionine, in cultured cardiomyocytes. YAP also upregulated ASC-1, a serine transporter, in cardiomyocytes, and YAP-induced increases in serine content in cardiomyocytes were decreased in the presence of Asc-1 knock-down. YAP-induced increases in cardiomyocyte cell size were inhibited in the presence of siRNA targeting Phgdh, Psat1, Psph, Shmt1 or Asc-1, suggesting that the increase in serine content plays an important role in mediating YAP-induced hypertrophy in cardiomyocytes. TAC increased binding of YAP and TEAD1 to the promoters of the SSP genes, whereas YAP-induced upregulation of PHGDH and PSAT1 was inhibited in the presence of TEAD1 downregulation. These results suggest that YAP directly promotes expression of genes involved in serine synthesis and uptake in cardiomyocytes, and that upregulation of the serine content plays an important role in mediating YAP-induced cardiac hypertrophy. - Source: PubMed
Publication date: 2026/06/05
Hu ChengchenZhai PeiyongSu XiaoyangRamoszepeda JacquelineChiles EricKhatimah Nurul GustiIkeda SoichiroKass David ASadoshima Junichi - Capsaicin, a natural compound, has demonstrated antitumor efficacy in estrogen receptor-positive breast cancer (ER-positive BC). However, its downstream molecular targets and mechanisms remain poorly understood, particularly those linked to metabolic reprogramming and immune modulation. This study aimed to identify capsaicin-responsive genes and explore their roles in ER-positive BC progression and tumor microenvironment remodeling. Bioinformatic analysis was performed on the GSE64155 dataset from GEO to screen differentially expressed genes (DEGs) in capsaicin-treated ER-positive BC. Functional enrichment (GO/KEGG) and protein-protein interaction (PPI) network analyses were performed to prioritize key genes. Experimental validation included qPCR and Western blotting to assess gene and protein expression in capsaicin-treated cells. Clinical relevance was evaluated using TCGA expression data, survival analysis (overall survival [OS], relapse-free survival [RFS], and distant metastasis-free survival [DMFS]), and immunohistochemistry (IHC) in BC tissues. Immune cell infiltration was analyzed via the CIBERSORT algorithm. SHMT2 and GARS were identified as the most significant capsaicin-responsive genes. Both genes were overexpressed in BC tissues and may be associated with a poor prognosis in patients with ER-positive BC. Capsaicin significantly reduced SHMT2 and GARS expression at the mRNA and protein levels. Immune infiltration analysis indicated that high SHMT2 and GARS expression may be associated with altered immune cell infiltration patterns. This study identifies SHMT2 and GARS as novel downstream targets of capsaicin in ER-positive BC and links their known oncogenic functions to a potential new mechanism underlying the antitumor effects of capsaicin. - Source: PubMed
Publication date: 2026/06/03
Zheng LongLi WenjinWang BingWu TaoHuang HaoHe YongchaoQu Wei - The progression of non-small cell lung cancer (NSCLC) is driven by metabolic plasticity and evasion of apoptotic surveillance, mechanisms that remain incompletely understood. Here, through integrated transcriptomic-metabolomic profiling, molecular interaction mapping, and functional validation, we unveiled a dual regulatory mechanism governed by the MTHFR/SLC25A26 axis that suppresses NSCLC. Clinical cohort analyses revealed concurrent downregulation of MTHFR and SLC25A26 in NSCLC tissues, which strongly correlated with poor prognosis. Mechanistically, MTHFR directly binds and stabilizes SLC25A26, whereas SLC25A26 accelerates SHMT2 degradation via the ubiquitin-proteasome pathway and concurrently suppresses AKT-driven MYB transcriptional activation. This coordinated disruption of serine/one-carbon metabolism and oncogenic signaling significantly inhibited tumor growth in patient-derived xenograft models. Crucially, we identified SLC25A26 as a mitochondrial transporter-ubiquitin adapter hybrid that destabilizes SHMT2 through ubiquitination, whereas its interaction with MTHFR prevents metabolic dysregulation induced by the C677T mutation. Our findings establish the MTHFR/SLC25A26 axis as a master regulator of metabolic-transcriptional crosstalk, providing a therapeutic framework for targeting enzyme stability and kinase signaling in NSCLC treatment.The MTHFR/SLC25A26 axis suppresses NSCLC progression through catalytic activity-dependent stabilization of SLC25A26 by MTHFR, where SLC25A26 functions as a ubiquitin adapter to degrade SHMT2 while concurrently repressing AKT-MYB-driven SHMT2 transcription; clinical downregulation of this axis predicts poor prognosis, and MTHFR overexpression inhibits tumor growth in vivo. - Source: PubMed
Publication date: 2026/06/01
Li LanYang YiRanWang ShiQingLi DanChen ChuMaoMu XinMeiWu JiaXinYuan Jin - We aimed to investigate the shared molecular pathways between Parkinson's disease (PD) and constipation using bioinformatics analysis. - Source: PubMed
Su JiehuaHuang KaixunJing XiunaLiu XiaohuanWen ChengGeng RulinLai ZhuoyingRuan ZhijiaZhan YiqiangLin DanyuTao Enxiang - Metabolic reprogramming is a hallmark of gastric cancer and is essential for sustaining rapid proliferation and malignant progression. The serine synthesis pathway (SSP), a key branch of glycolysis coupled to one-carbon metabolism (OCM), plays a central role in nucleotide biosynthesis, redox homeostasis, and epigenetic regulation. Although aberrant SSP activation has been implicated in gastric cancer, its upstream regulatory mechanisms remain poorly defined. Long non-coding RNAs (lncRNAs) have emerged as critical modulators of oncogenic signaling and metabolism. This study aimed to elucidate the role of the lncRNA SNHG12 in gastric cancer progression and to determine whether it drives metabolic reprogramming through the Wnt/β-catenin-SSP axis. - Source: PubMed
Publication date: 2026/04/30
Zhang NianjieLi TaolangWen Kunming