Ask about this productRelated genes to: SMYD1 Blocking Peptide
- Gene:
- SMYD1 NIH gene
- Name:
- SET and MYND domain containing 1
- Previous symbol:
- -
- Synonyms:
- BOP, ZMYND22, KMT3D
- Chromosome:
- 2p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-04-29
- Date modifiied:
- 2018-11-19
Related products to: SMYD1 Blocking Peptide
Related articles to: SMYD1 Blocking Peptide
- Anthracyclines are potent chemotherapeutic agents known for their efficacy in treating various cancers via inhibition of topoisomerase II alpha (TOP2A). However, their clinical use is limited due to cardiotoxicity, primarily attributed to off-target inhibition of topoisomerase II beta (TOP2B) in cardiomyocytes. The well-accepted mechanism involves TOP2B inhibition as a key driver of this toxicity. Here, we identify a novel mechanism of anthracycline-induced cardiotoxicity (AIC) involving upregulated TOP2B expression and its direct impact on cardiomyocyte function. Our data show that doxorubicin significantly increased TOP2B protein levels in cardiomyocytes in AIC mouse model. The cardiomyocyte-specific, tamoxifen-inducible TOP2B transgenic mice exhibited pathophysiological features consistent with doxorubicin-induced cardiotoxicity, even without exposure to anthracyclines. Additionally, we discovered that TOP2B binds to SMYD1, a histone methyltransferase critical for muscle cell function. Mutations in SMYD1 are known to cause cardiomyopathy and heart failure in humans, and loss of Smyd1 in mice results in a phenotype resembling AIC. More importantly, TOP2B ASO pretreatment can succussfully prevent the AIC in TOP2B transgenic mice and AIC mouse models. Our findings reveal a novel role for TOP2B in AIC, demonstrating that its upregulation disrupts SMYD1 function in cardiomyocytes, contributing to cardiotoxicity. This study also highlights the therapeutic potential of targeting TOP2B using ASO for preventing AIC in cancer patients, offering new insights into cardioprotective strategies. - Source: PubMed
Publication date: 2026/05/08
Wang QingzhuZhang WanyingChen JosephineStenson Kate TParsai ShikhaParthasarathy Prerana BangaloreLiu Chia-FengGarrett ThomasLin JungHou AnlinShimpi Riya AGu EricYin MeiShannon LoganJohnson SadieWillard Belinda BRodriguez E ReneAndrojna CharlieMoudgil RohitSun YilunYu Jennifer SNguyen ChristopherAlban Tyler JChan Timothy APrasad Sathyamangla V NagaTang W H WilsonLin JianhongZhao Jianjun - Sirtuin 1 () is known to regulate stem cell differentiation and cardiomyocyte function, yet its specific role and mechanism in human embryonic stem cell (hESC) differentiation into cardiomyocytes remain unclear. This study aimed to elucidate the functional contribution and molecular pathway of in cardiomyogenesis. : A knockout (/) hESC line was generated using CRISPR-Cas9 technology. The expression of key differentiation markers was analyzed by RT-qPCR at days 6, 8, and 9. The underlying mechanism was investigated through integrated RNA-sequencing (RNA-seq) analysis and dual-luciferase reporter assays. : deletion significantly downregulated the expression of mesodermal (TBX6, KDR), cardiac precursor (NKX2.5, TBX5), and mature cardiomyocyte (cTNT, Hand2) markers. Mechanistically, a competing endogenous RNA (ceRNA) axis, LncRNA XR_951230.1/miR-3663-3p/SMYD1, was identified. knockout reduced XR_951230.1 expression, which consequently elevated miR-3663-3p activity and suppressed its target gene SMYD1. : These findings indicate that is essential for promoting hESC differentiation into cardiomyocytes, potentially via the XR_951230.1/miR-3663-3p/SMYD1 pathway. This study provides new insights into the regulatory network of stem cell-based cardiomyogenesis and suggests potential targets for stem cell-based cardiac disease therapy. - Source: PubMed
Publication date: 2026/02/27
Li ChengyuMahemuti MairepatiMaimaiti YusupujiangWang TingZhang XinJiapaer Zeyidan - Histone methyltransferase SET and MYND domain-containing 1 (SMYD1), a member of the SMYD family, catalyzes the methylation of lysine residues on histone proteins. This modification is pivotal in regulating chromatin structure and gene expression, influencing processes such as cell proliferation, differentiation, and development. Primarily expressed in muscle tissues, SMYD1 plays a crucial role in muscle development and function. However, accumulating evidence suggests its involvement in the progression of various diseases, including cancer, cardiovascular diseases, and metabolic disorders. By modulating key signaling pathways and gene expression profiles, SMYD1 affects cellular processes such as cell cycle regulation, apoptosis, and inflammation. This review aims to explore the multifaceted roles of SMYD1 in disease progression, highlighting its potential as a therapeutic target. Understanding the molecular mechanisms underlying the effects of SMYD1 will be essential for developing strategies to manipulate its activity for disease prevention and treatment. - Source: PubMed
Publication date: 2026/02/09
Duan LingqianLou YangHuang KanPan KailingChen Xianguo - Stress urinary incontinence (SUI) remains a significant clinical challenge due to the lack of strategies that simultaneously address muscle degeneration, neurogenic atrophy, and vascular deficits. Here, we report an innovative injectable system that combines a thermo-responsive poly(N-isopropylacrylamide)-COOH/leucine/decellularized extracellular matrix hydrogel with adipose-derived stem cells (ADSCs) pre-programmed by zeolitic imidazolate framework-8/polyethylene glycol 200@magnesium (ZIF-8/PEG200@Mg) nanoparticles. In vitro, programmed ADSCs exhibit enhanced neurogenic differentiation, while the hydrogels support robust myogenic activity and cell viability. In a female rat model of SUI-chosen to reflect the higher prevalence of SUI in women-the composite system leads to a marked improvement in leak point pressure (LPP) and restores urethral sphincter function. Mechanistic analyses reveals upregulation of muscle regeneration (e.g., Myoz1, Smyd1) and neurogenesis/neuromuscular junction stabilization (NMJ) stabilization genes (e.g., Dok7, Musk), highlighting a coordinated multi-lineage regenerative process. This work establishes an integrated regeneration-plus-support injectable strategy, offering a regenerative medicine-based approach that surpasses conventional bulking or sling therapies for SUI. - Source: PubMed
Publication date: 2025/09/25
Fang WenzhuoDu XuanYang RanxingLiu MengYang MingJin YangwangGao GuoFu QiangWang Ying - The SMYD family comprises a distinct class of lysine methyltransferases (KMTases) that methylate both histone and non-histone proteins. Among its five members (SMYD1-5), SMYD1 has been identified as a cardiac and skeletal muscle-specific KMTase that interacts with Myosin, in coordination with Unc45b and Hsp90a, to regulate thick filament assembly. However, the precise mechanism by which SMYD1 orchestrates Myosin assembly remains largely unknown. Here, we demonstrate that SMYD1 physically associates with the N-terminal region of several myosin heavy chain (MyHC) isoforms and specifically catalyzes the mono-methylation of MyHC at lysine 35 (K35). Methylated MyHC is correctly incorporated into sarcomeres, whereas unmethylated MyHC in Smyd1-deficient zebrafish undergoes degradation via the ubiquitin-proteasome system (UPS), leading to defective thick filament assembly. Although UPS inhibition with MG132 restores Myosin levels in Smyd1-deficient zebrafish embryos, proper thick filament assembly remains impaired due to the absence of K35 MyHC mono-methylation. Similar to zebrafish striated muscle cells, SMYD1-mediated MyHC methylation is essential for thick filament assembly but also homeostasis in human cardiomyocytes, indicating a conserved cross-species mechanism of Myosin regulation, first described nearly 40 years ago. Further research is now required to explore the therapeutic potential of targeting this pathway in cardiomyopathies and skeletal muscle disorders. - Source: PubMed
Publication date: 2025/09/17
Diofano FedericaAmadi ChidinmaHartmann LarissaGahr Bernd MWeinmann-Emhardt KarolinaRottbauer WolfgangJust Steffen