PRMT5
- Known as:
- PRMT5
- Catalog number:
- Y214157
- Product Quantity:
- 200ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- PRMT5
Related genes to: PRMT5
- Gene:
- PRMT5 NIH gene
- Name:
- protein arginine methyltransferase 5
- Previous symbol:
- HRMT1L5, SKB1
- Synonyms:
- SKB1Hs
- Chromosome:
- 14q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-06-18
- Date modifiied:
- 2017-12-15
Related products to: PRMT5
Related articles to: PRMT5
- Homozygous loss of the 9p21 locus encompassing CDKN2A, CDKN2B, and MTAP is the most frequent copy number alteration across tumor types, making it a promising target for precision medicine strategies. To explore drug vulnerabilities exposed by this loss, we generated 9p21 locus isogenic bladder cancer (BLCA) cell models to perform a multiparametric drug screen, testing 2,349 compounds. We identified cytarabine and methotrexate as significantly more effective in the 9p21 compromised BLCA cells. Analysis of morphological alterations further supported a genotype-specific activity of nucleoside analogs, nominating gemcitabine as a drug with greater efficacy in this context. To further exploit MTAP loss, we explored drug combinations targeting MTAP synthetic lethal partners, PRMT5 and MAT2A. Synergy between cytarabine and inhibitors of PRMT5 (MRTX1719) and MAT2A (AG-270) was mediated by a differential activation of DNA damage and replication stress markers, suggesting an exploitable vulnerability. In fact, rational drug combinations with ATR/CHK1 pathway inhibitors increased efficacy while maintaining 9p21-specificity. Finally, we confirmed the effectiveness of these combinations in cell models of pancreatic adenocarcinoma and pleural mesothelioma, two tumor types with high prevalence of MTAP loss and, most notably, in bladder cancer patient-derived organoids, underscoring the strong translational potential of our findings. - Source: PubMed
Publication date: 2026/04/18
Bevilacqua RiccardoGasperini PaolaCantore ThomasMacedo-Silva CatarinaPancher MichaelRadić MartinaYue HaiyanQuaini OrsettaFedrizzi TarcisioGatto PamelaSeiler RolandKiss BernhardAdami ValentinaLorenzin FrancescaKruithof-de Julio MariannaFaltas Bishoy MorrisDemichelis Francesca - Protein arginine methyltransferase 5 (PRMT5) is overexpressed in B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). While PRMT5 is known to regulate multiple oncogenic pathways, including PI3K-AKT signaling, its role in lipid metabolism and ferroptosis, a regulated, iron-dependent cell death driven by lipid peroxidation, remains poorly understood. Here, we identify a novel role for PRMT5 in suppressing ferroptosis in DLBCL and MCL cells through upregulation of SLC7A11, which imports cystine for glutathione (GSH) biosynthesis. This effect is mediated by the AKT-MYC-ATF5 signaling axis. ATF5, a MYC-regulated transcription factor overexpressed in these lymphomas, induces SLC7A11 expression. In addition, ATF5 promotes the expression of ATF4, another key regulator of the ferroptotic response, which forms heterodimers with ATF5 to further reinforce this regulatory network. PRMT5 inhibition sensitizes lymphoma cells to ferroptosis inducers such as dimethyl fumarate (DMF), an electrophile that irreversibly depletes GSH via succination. Notably, combined treatment with the PRMT5 inhibitor GSK3326595 and DMF synergistically enhances anti-tumor activity in a patient-derived xenograft (PDX) model. These findings reveal a previously unrecognized PRMT5-ATF5-SLC7A11 axis that drives ferroptosis resistance in B-cell lymphomas and provide a strong rationale for targeting PRMT5 to potentiate ferroptosis-based therapies in relapsed or refractory disease. - Source: PubMed
Publication date: 2026/04/17
Liu YunxiaChen RuoyuGao XiaoyueZhu FenNi QinyuBates Paul DWu SunnyZai ZhuoyanObernberger Victoria AWeerawardhene KavinuTourdot Taylor KPetta SophieConyers Madison JCapitini Christian MRui Lixin - Despite multimodal therapy of surgical resection, radiation, and chemotherapy, glioblastoma patients show a dismal prognosis. Protein Arginine Methyltransferase 5 (PRMT5) is overexpressed in glioblastoma, and its inhibition imparts an anti-tumor effect. Tumor cells invariably develop resistance to Temozolomide (TMZ), the standard chemotherapeutic agent for glioblastoma. However, the mechanistic role of PRMT5 in treatment-resistant glioblastoma is unknown. Patient-derived glioma stem-like cells (GSCs), treated with PRMT5 inhibitor (LLY-283) or transfected with PRMT5-target-specific siRNA, were treated with TMZ and subjected to in vitro functional and mechanistic studies. The intracranial mouse xenograft model was used to test the in vivo antitumor efficacy of combination treatment. We found that PRMT5 inhibition increased the cytotoxic effect of TMZ in GSCs. Unbiased transcriptomic profiling revealed negative enrichment of DNA damage repair pathways, with prominent suppression of the Fanconi anemia (FA) pathway. PRMT5 inhibition abrogated the TMZ-induced G2/M cell cycle arrest. Importantly, combination treatment increased the DNA double-strand breaks (γH2AX foci) and enhanced the DNA damage (comet assay). Specifically, the LLY-283 treatment blocked the FA pathway-mediated homologous recombination repair in GSCs. In vivo, the LLY-283 and TMZ combination significantly curbs tumor growth and prolongs the survival of tumor-bearing mice. Furthermore, compared to monotherapy, there was a significant reduction in the proliferation marker Ki-67, while the apoptosis marker cleaved caspase 3 and the DNA damage response marker γH2AX were upregulated. Collectively, these findings identify PRMT5 as a critical regulator of the FA pathway in glioblastoma and demonstrate that PRMT5 inhibition potentiates TMZ efficacy by disrupting FA-dependent homologous recombination repair, indicating that the combination of PRMT5 inhibition and TMZ could be a novel therapeutic strategy for glioblastoma. - Source: PubMed
Publication date: 2026/04/15
Onishi ShumpeiJayamohan SridharanChowdhury AshisRivas SarahOtani YoshihiroErtekin CelineBryant Jean-PaulMurphy Sara ARivera-Caraballo Kimberly AWalbridge StuartSisay BayuMaric DraganElkahloun AbdelJohnson KoryBrown Desmond AHeiss John DShah Ashish HLee Tae JinKumbar Sangamesh GYoo Ji YoungBrenner Andrew JKaur BalveenSareddy Gangadhara RBanasavadi-Siddegowda Yeshavanth Kumar - Thymic carcinoma (TC) is a rare, aggressive subset of thymic epithelial tumors (TETs) with a poor prognosis and limited treatment options. Representing approximately 15-20% of TETs, TC is distinct from thymoma in its histopathologic features, lack of paraneoplastic autoimmune syndromes, and more complex genomic landscape. Surgical resection remains the primary modality for early-stage disease, while platinum-based chemotherapy forms the cornerstone of treatment for advanced or unresectable TC. Advancements in targeted therapies have expanded therapeutic options, resulting in improved clinical efficacy, especially in tumors with high angiogenic activity or specific mutations (e.g., Kit). Immune checkpoint blockade (ICB) has shown activity in TC, with response rates around 20%, and is being explored in combination with chemotherapy, anti-angiogenic agents, and CTLA-4 blockade. Combinatorial strategies have demonstrated enhanced response rates but require vigilant management of immune-related adverse events. Novel therapeutic approaches are emerging, including PRMT5 inhibitors in MTAP-deficient tumors, TROP-2-directed antibody-drug conjugates (e.g., sacituzumab govitecan), and chimeric antigen receptor (CAR) T-cell therapies targeting mesothelin. Bispecific agents such as bintrafusp alfa and ivonescimab, which co-target various pathways, offer innovative strategies. Despite these advances, TC remains a challenging malignancy with no standardized treatment algorithm. Collaborative efforts across institutions will be essential to accelerate progress and improve outcomes in this rare disease. - Source: PubMed
Publication date: 2026/03/18
Maniar RohanLoehrer Patrick J - Dysregulated HSP90AA1 chaperone activity is a hallmark of multiple cancers; however, its post-translational regulation in esophageal squamous cell carcinoma (ESCC) remains poorly defined. Here, we defined PRMT5-dependent symmetric dimethylation of HSP90AA1 at arginine 182 (R182) as a critical molecular switch driving ESCC progression. HSP90AA1 physically interacted with PRMT5, and genetic or pharmacological inhibition of PRMT5 markedly reduced HSP90AA1 R182 methylation, accompanied by suppression of epithelial-mesenchymal transition (EMT) programs. HSP90AA1 depletion significantly impaired ESCC cell proliferation, migration, and invasion, inducing cell-cycle arrest and EMT reversal. In rescue experiments, re-expression of wild-type HSP90AA1 restored malignant phenotypes both in vitro and in vivo, whereas the methylation-deficient R182A mutant failed to do so. Mechanistically, R182 methylation stabilized key EMT transcription factors, thereby establishing a methylation-chaperone-EMT regulatory axis. Clinically, HSP90AA1 was markedly overexpressed in ESCC tissues and correlated with poor patient outcomes. Therapeutically, dual targeting of PRMT5 and HSP90AA1 exerted potent antitumor effects, suppressing clonogenicity and invasion in vitro and significantly reducing tumor burden in both cell-derived and patient-derived xenograft models. Collectively, these findings established the PRMT5-HSP90AA1 R182 methylation axis as a targetable vulnerability in ESCC and provided a strong rationale for biomarker-driven combinatorial therapeutic strategies. - Source: PubMed
Publication date: 2026/04/09
Chen TangbingLv YilvWang JingYuan YonggangXu KuanShi MinjunLi WangYe Bo