Ask about this productRelated genes to: SMYD2 antibody
- Gene:
- SMYD2 NIH gene
- Name:
- SET and MYND domain containing 2
- Previous symbol:
- -
- Synonyms:
- HSKM-B, ZMYND14, KMT3C
- Chromosome:
- 1q32.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-04-28
- Date modifiied:
- 2014-11-19
Related products to: SMYD2 antibody
Related articles to: SMYD2 antibody
- The journal retracts the article titled "The Lysine Methyltransferase SMYD2 Is Required for Definite Hematopoietic Stem Cell Production in the Mouse Embryo" [...]. - Source: PubMed
Publication date: 2026/09/15
Edwards Melissa ABrown Mark AAlshiraihi IlhamJarrell Dillon KTucker Haley O - Among the more than 90 identified genetic risk loci for late-onset Alzheimer's disease (AD) and related dementias, the apolipoprotein E (APOE) gene ɛ2/ɛ3/ɛ4 polymorphisms remain the longstanding benchmark for genetic disease risk with a consistently large effect across studies. Despite this massive signal, the exact mechanisms by which ɛ4 increases and ɛ2 decreases dementia risk remain poorly understood. Notably, recent trials of anti-amyloid therapies suggest less efficacy and higher risks of severe side effects in ε4 carriers, hampering the treatment of those with the highest unmet need. To improve our understanding of the genetic architecture of AD in the context of its main genetic driver, we performed genome-wide association studies (GWASs) stratified by ε4 and ε2 carrier status. HP1BP3, SLC50A1, PTPRC, NPAS3, DDHD1, CHST9, SMYD2, PRAMEF1 and GFRA1 emerged as new genomic signals for AD risk, appearing only when stratified by APOE carrier status. DDHD1 appeared especially promising, showing protective effects in ε4 carriers, being identified as an expression quantitative trait locus and being involved in rare neuronal diseases. Such APOE-stratified insights may help understand and overcome side effects, inform clinical trial enrollment strategies, and create the scientific basis for targeted, mechanism-driven therapies in neurodegenerative diseases. - Source: PubMed
Publication date: 2026/09/14
Thomassen Jesper QvistLeonard HamptonUlms BrittanyGrenier-Boley BenjaminHeikkinen SamiGarcia-González PabloCastillo-Morales AtahualapaKikuchi MasatakaGim JungsooCao HanKüçükali FahriAmin NajafYoon Dabinde Rojas ItziarAlvarez Jerez PilarAlvarez VictoriaArosio BeatriceBellenguez CélineBergh SverreBillingsley KimberleyBlauwendraat CornelisBoada MerceBorroni BarbaraBossù PaolaBullido María JDaniele AntonioCarracedo Ángelde Mendonça AlexandreCookson MarkDeckert JürgenDichgans MartinDjurovic SrdjanDols-Icardo OriolDufouil CaroleDüzel EmrahEscott-Price ValentinaFladby TormodFratiglioni LauraFu Amy K YGalimberti DanielaGarcía-Alberca Jose MariaGiedraitis VilmantasGarcia-Ribas GuillermoGraff CarolineGrimmer TimoGrünblatt EdnaHanon OlivierHausner LucreziaHeilmann-Heimbach StefanieHort JakubJessen FrankJensen KendallJonson CarolineKim YoontaeKuznetsov NicoleLeinonen VilleLipponen AnssiLuo JiaoMakarious MaryMartiskainen HennaMasullo CarloMecocci PatriziaMehrabian ShimaMir PabloMiyashita AkinoriMoebus SusanneMok Kin YMolina Porcel LauraMoreno FerminNacmias BenedettaParnetti LucillaPastor PauPérez-Tur JordiPeters OliverPijnenburg Yolande A LPiñol-Ripoll GerardPopp JuliusRainero InnocenzoReal Luis MRiedel-Heller SteffiRodriguez-Rodriguez EloyRongve ArvidRossi GiacominaRoyo Jose LuisRujescu DanSaltvedt IngvildSáez María EugeniaSánchez-Valle RaquelSanchez-Garcia FlorentinoSandau NicolaiScarmeas NikolaosScheffler KatjaScherbaum NorbertSchneider AnjaSelbæk GeirSeripa DavideSolfrizzi VincenzoSpallazzi MarcoSquassina AlessioStordal EysteinTesi NiccolóTremolizzo LucioTripathi Kumar Pvan der Flier Wiesje MWilliams JulieWiltfang JensAarsland DagSingleton Andrew BAmouyel PhilippeDebette StéphanieTsolaki MagdaNicolas Gaelvan der Lee SvenHolstege HenneFernandez Maria VictoriaKehoe Patrick GavinSleegers KristelIngelsson MartinGhidoni RobertaAndreassen Ole AHolmans Peter ASánchez-Juan PascualSims RebeccaIp Nancy YLee Kun HoIkeuchi TakeshiRamirez AlfredoRuiz AgustinHiltunen MikkoLambert Jean-Charlesvan Duijn CorneliaNalls MikeFrikke-Schmidt Ruth - Cancer cells frequently acquire adaptive resistance to targeted therapies; however, strategies capable of concurrently overcoming treatment tolerance and reactivating cell death pathways are currently lacking. Here, we investigated the dual role of ferredoxin 1 (FDX1) in modulating both multikinase inhibitor (MKI) sensitivity and cuproptosis susceptibility in hepatocellular carcinoma (HCC), and sought to develop a therapeutic approach for reversing resistance. HCC models, both in vitro and in vivo, were employed to investigate the role of FDX1 in MKI resistance and cuproptosis evasion. Polysome profiling, SunTag translation reporters, CRISPR-Cas9 mutagenesis, and mass spectrometry were employed to delineate the underlying mechanisms. A codelivery nanoliposome system was engineered and tested in orthotopic HCC models. Prolonged exposure to MKIs led to the down-regulation of FDX1 protein levels, resulting in MKI resistance and cuproptosis tolerance in HCC both in vitro and in vivo. Mechanistically, we found that MKIs inactivated protein kinase B (PKB, also known as AKT)-mechanistic target of rapamycin (mTOR) signaling, thereby suppressing the SET and MYND domain-containing protein 2 (SMYD2)-mediated methylation of YTH domain family protein 1 (YTHDF1) at lysine 515 (K515). Hypomethylated YTHDF1 was degraded via next to BRCA1 gene 1 protein (NBR1)-dependent autophagy, leading to the repression of N6-methyladenosine modification-dependent translation of mRNA. FDX1 deficiency drove MKI resistance by reactivating AKT survival signaling while impairing cuproptosis through reduced divalent copper ions (Cu) to monovalent copper ions (Cu) conversion and the loss of protein lipoylation. Additionally, restoring FDX1 expression through knockdown or overexpression overcame MKI resistance and resensitized HCC cells to cuproptosis. Finally, a nanoliposomal system, super cuproptosis detonator liposome, designed for the codelivery of small interfering RNA, a copper ionophore, and sorafenib restored FDX1-dependent cuproptosis and exhibited marked anti-HCC efficacy, suppressing HCC growth in vivo. MKIs suppressed SMYD2-mediated YTHDF1 methylation at K515 via the inactivation of AKT-mTOR signaling. This led to the inhibition of translation, resulting in AKT signaling reactivation and protein lipoylation impairment, effects that contributed to both MKI resistance and cuproptosis tolerance in HCC. Overcoming MKI resistance and resensitizing cells to cuproptosis by targeting NBR1-mediated YTHDF1 degradation using a nanoliposomal codelivery system represents a promising strategy for HCC treatment. - Source: PubMed
Publication date: 2026/09/11
Wang WeikaiJiang XinChen XiaonaLiang KaiyuChen MiaoqinLu KaizhongWei QiWu YuchenZhu LiyuanChen YuanHou TianlunLuo JingfengLi ChentaoWang XianJin HongchuanFeng Lifeng - The progression and resistance to targeted therapy, including pazopanib, frequently lead to poor prognosis in clear cell renal cell carcinoma (ccRCC) patients. However, the underlying molecular mechanisms of these processes remain unclear. - Source: PubMed
Publication date: 2026/07/29
Sun YunWang MengyaoSong HaoranWu YiHe YingxiaMa FuminLiang YuxuanZhang LishuoGong JiananRen MinghuaZhong ZhaohuaZhao WenranDing Beichen - Colorectal cancer (CRC) is the second most common cancer-causing death in the United States. The Mediterranean diet, rich in extra-virgin olive oil (EVOO), is associated with a lower risk of colorectal cancer (CRC). Earlier studies reported -(-)-oleocanthal (OC), the major EVOO phenolic, to be effective in CRC progression and recurrence suppression in a subcutaneous xenograft model by targeting the SMYD2-EZH2/c-MET signaling axis and favorably modulating gut microbiota (GM). However, lead validation in an orthotopically xenografted model that mimics the tumor microenvironment is yet to be achieved. The GM contribution to OC anti-CRC activity remains unknown. We used an orthotopic intra-cecally xenografted nude mouse model to validate OC anti--mutant CRC activity and assessed the contribution of OC GM modulation to this activity using an oral antibiotic depletion strategy. Daily oral 10 mg/kg OC impressively suppressed -mutant CRC HCT-116-Luc progression and metastasis more effectively than intraperitoneal administration 3×/week. By contrast, GM depletion with a broad-spectrum antibiotics cocktail (ABC) partially attenuated this activity, suggesting GM contribution to OC anti-CRC activity. Thus, fecal microbiota transplantation (FMT) was conducted using fresh daily oral fecal GM treatments collected from 20 mg/kg OC-dosed nude mouse donors. A week before FMT dosing, orthotopic HCT-116-Luc tumor-bearing recipient mice were subjected to GM depletion using daily oral ABC dosing. Recipient mice treated with FMT from OC-treated donors exhibited dramatic >99% reductions in primary and near-complete suppression of multi-organ metastatic tumor burden versus FMT controls. Collectively, oral OC is validated as an effective anti--mutant CRC lead. Future clinical trials can validate its anti-CRC potential in a human model. - Source: PubMed
Publication date: 2026/08/11
Tarun Md Towhidul IslamEbrahim Hassan YEl Sayed Khalid A