Ask about this productRelated genes to: GLRX2 Blocking Peptide
- Gene:
- GLRX2 NIH gene
- Name:
- glutaredoxin 2
- Previous symbol:
- -
- Synonyms:
- GRX2, bA101E13.1
- Chromosome:
- 1q31.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-08-24
- Date modifiied:
- 2015-11-13
Related products to: GLRX2 Blocking Peptide
Related articles to: GLRX2 Blocking Peptide
- Protein tyrosine phosphatases (PTPs) counteract receptor tyrosine kinase (RTK) signaling. Inhibition of PTPs by oxidation can be reversed by cytosolic thioredoxin (TXN), but less is known about regulation of PTPs by glutathione (GSH)-driven glutaredoxins (GLRXs). Here, we thus assessed GLRX1, GLRX2, and/or TXN1 in regulation of CO/bicarbonate- and HO-mediated oxidation of the physiologically important PTP1B. GLRXs and TXN1 synergistically maintained PTP1B activity, and modulating cellular levels of either GLRX1, GLRX2, or TXN1 gave strong effects on phosphorylation cascades triggered by epidermal growth factor (EGF) or platelet-derived growth factor (PDGF). Furthermore, transient intracellular interactions of PTP1B with GLRX1, GLRX2, and TXN1 were discovered within minutes after stimuli with either PDGF or EGF, coinciding with control of the corresponding RTK-driven phosphorylation cascades. We conclude that TXN1 and GLRXs are key regulators of PTP1B activity and thus control cellular responses to RTK stimulation. - Source: PubMed
Publication date: 2026/04/10
Coppo LuciaZhao WenchaoCheng QingScholz Axel TobiasArnér Elias S JDagnell Markus - Breast cancer is highly heterogeneous, with multiple subtypes that differ in molecular and clinical characteristics. It remains the most common cancer among women worldwide. We conducted a hypothesis-generating study using a bioinformatics approach in order to identify potential prognostic biomarkers for breast cancer patients across multiple molecular subtypes. Given the influential role of the transforming growth factor beta (TGFB) pathway in shaping the immune microenvironment, we focused on the isoform, transforming growth factor beta 2 (), which is upregulated in tumors, to identify -dependent and -independent biomarkers for breast cancer patients' overall survival (OS) responses. We evaluated the impact of mRNA expression, in conjunction with other potential prognostic markers, on overall survival (OS) in breast cancer patients using The Cancer Genome Atlas (TCGA) and KMplotter databases. We employed a multivariate Cox proportional hazards model to compute hazard ratios (HRs) for mRNA expression, integrating an interaction term that accounts for the multiplicative relationship between and marker gene expressions while controlling age at diagnosis and cancer subtype and differentiating between patients receiving chemotherapy alone and those undergoing alternative therapeutic interventions. We used the KMplotter database to confirm -independent prognostic markers from TCGA data. In cases dependent on , increased mRNA expression of alongside higher levels of , , , , , , or was correlated with improved OS among breast cancer patients, of which four genes were upregulated in tumor tissues (, , , ). Future studies will be required to confirm breast cancer patients could improve OS outcomes for patients expressing high levels of and the marker genes in prospective clinical trials. Additionally, multivariate analysis revealed that the elevated expression of six genes (, , , , , ) were correlated with increases in HR, independent of mRNA expression; all except were identified as druggable targets. Future investigations assessing protein expression in breast cancer tumors to confirm the results of our retrospective analysis of mRNA levels will determine whether the protein products of these genes represent viable therapeutic targets. Protein-protein interaction (STRING) analysis indicated that TGFB2 is associated with EGFR and MYC from the PAM50 breast cancer gene signature. These findings suggest that correlation of -related markers could potentially complement the PAM50 signature in the assessment of OS prognosis in breast cancer patients, but further validation of the TGFB2/EGFR/MYC proteins in tumors is warranted. - Source: PubMed
Publication date: 2025/11/29
Qazi SanjiveRichardson StephenPotts MikeMyers ScottTrieu Vuong - Patients with acute myeloid leukemia (AML) have a poor 5-year survival rate, highlighting the need for the identification of new approaches to target this disease. AML is highly dependent on glutathione (GSH) metabolism for survival. Although the metabolic role of GSH is well characterized in AML, the contribution of protein glutathionylation, a reversible modification that protects protein thiols from oxidative damage, remains largely unexplored. Therefore, we sought to elucidate the role of protein glutathionylation in AML pathogenesis. Here, we demonstrate that protein glutathionylation is essential for AML cell survival. Specifically, the loss of glutaredoxin 2 (GLRX2), an enzyme that removes GSH modifications, resulted in selective primary AML cell death while sparing normal human hematopoietic stem and progenitor cells. Unbiased proteomic analysis revealed increased mitochondrial protein glutathionylation upon GLRX2 depletion, accompanied by mitochondrial dysfunction, including impaired oxidative phosphorylation, reduced mitochondrial membrane potential, and increased opening of the mitochondrial permeability transition pore (mPTP). Further investigation identified adenosine triphosphate synthase subunit O (ATP5PO), a key regulator of mPTP opening and a component of the ATP synthase complex, as a critical GLRX2 target. Disruption of ATP5PO glutathionylation partially restored mPTP function and rescued AML cell viability after GLRX2 depletion. Moreover, both genetic and pharmacological inhibition of mPTP opening restored the leukemic potential of primary AML specimens in the absence of GLRX2. By disrupting glutathionylation-dependent mitochondrial homeostasis, this study reveals a novel vulnerability in AML that could inform future therapeutic strategies. - Source: PubMed
Ling TianyiO'Brien CristianaSt-Germain Jonathan RRondeau VincentShi MaryBerman Jacob MCepa AdriannaSaez Raez PaulaWunderlich MarkCarter Katharine MStillwell CodySexton ChristinaCulp-Hill RachelReisz Julie AAdeel Saeer AZeng Andy G XBansal SurajTsao EmilyChen He TianDick John EMinden Mark DArruda AndreaAmaya Maria LTikhonova Anastasia NHope Kristin JD'Alessandro AngeloRaught BrianJones Courtney L - Bioavailable testosterone (BAT), a critical factor for reproductive, metabolic, and psychological health, is primarily regulated by sex hormone-binding globulin (SHBG). However, the molecular mechanisms driving SHBG-mediated regulation of BAT remain unclear. Identifying key protein regulators offers promising therapeutic opportunities for testosterone-related disorders. We conducted a comprehensive proteome-wide Mendelian randomization (PWMR) and colocalization analysis using large-scale pQTL and GWAS datasets. Mediation MR assessed SHBG's role in regulating BAT, and functional enrichment, protein interaction networks, phenome-wide association studies (PheWAS), and drug prediction were performed to explore therapeutic relevance and safety. We identified 36 proteins that influence BAT via SHBG mediation. Among them, five proteins (MAX, TXNL4B, GLRX2, F13B, SNUPN) showed strong or moderate colocalization with BAT, suggesting shared genetic regulation. MAX and TXNL4B increased BAT by reducing SHBG, while GLRX2, F13B, and SNUPN decreased BAT via elevated SHBG levels. PheWAS suggested potential risks for GLRX2 (depression) and TXNL4B (lipid disorders). Drug and compound prediction highlighted compounds, including cardiac glycosides, antioxidants, and endocrine-disrupting chemicals, targeting these proteins. Our findings reveal novel protein regulators of testosterone bioavailability through SHBG and provide a framework for developing targeted therapeutics. This integrative approach may support safer, more precise treatment strategies for testosterone-related metabolic and endocrine disorders. - Source: PubMed
Publication date: 2025/10/24
Hong Yanggang - The bladder is continuously exposed to oxidative and mutagenic agents. Such chemicals are metabolized, filtered by the kidneys, and excreted in the urine. Not surprisingly, urothelial bladder cancer (UBC) is the 9th most common cancer worldwide. This study investigates whether the C > T (rs912071) polymorphism in the Glutaredoxin 2 (GLRX2) gene, oxidative stress marker levels, and GLRX2 expression are associated with prognosis and recurrence in 341 patients with UBC. Gene expression data were compared to those available in TCGA. The TT genotype (OR = 2.475, p = 0.017) was positively associated with the risk of 1-year recurrence. Hypertensive patients carrying the CT genotype presented a reduced risk for recurrence (OR = 0.460, p = 0.047) and high-grade tumors (OR = 0.188, p = 0.001). Lipid peroxidation and nitric oxide metabolites (NOx) levels were higher in patients than in controls and in patients carrying the TT genotype. Tumor tissues and invasive tumors had higher GLRX2 expression, confirming the TCGA findings. DepMap analysis identifies GLRX2 as a valuable tool enabling personalized treatments for UBC patients. Our results showed that the TT genotype of rs912071 is associated with an increased risk of recurrence and high oxidative stress. In contrast, the CT genotype may protect against disease recurrence in patients with UBC cancer. - Source: PubMed
Publication date: 2025/09/30
Silva Isabely MVacario Beatriz G LMaraslis Flora TKoike AlexsandroSimonato Maria E PCoradi CarolinaFernandes Alvaro JSimão Andréa N CLozovoy Marcell A BBarcelos Gustavo R MFalco Mateus LGuembarovski Roberta LosiPanis CarolinaSerpeloni Juliana Mara