Ask about this productRelated genes to: GADD45G protein
- Gene:
- GADD45G NIH gene
- Name:
- growth arrest and DNA damage inducible gamma
- Previous symbol:
- -
- Synonyms:
- DDIT2, GADD45gamma, GRP17, CR6
- Chromosome:
- 9q22.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-09-06
- Date modifiied:
- 2016-10-05
Related products to: GADD45G protein
Related articles to: GADD45G protein
- Euchromatic histone-lysine N-methyltransferase 2 (EHMT2) has been implicated in cardiovascular diseases, yet its role in vascular remodeling remains incompletely understood. Here we investigated the contribution of EHMT2 to vascular smooth muscle cell (VSMC) proliferation, migration and neointima formation following vascular injury using carotid artery injury models and in vitro VSMC studies. Transcriptomic (RNA sequencing) and epigenomic (CUT&Tag) profiling revealed that EHMT2 levels were elevated in injured arteries and growth-stimulated VSMCs, whereas EHMT2 deletion attenuated injury-induced neointima formation. Mechanistically, EHMT2 methyltransferase activity promoted VSMC proliferation and migration, with pathway analyses implicating cell cycle and growth programs as major downstream targets. We further identified GADD45G as a critical EHMT2-regulated gene characterized by H3K9me2 enrichment, and demonstrated that GADD45G enforced G1-phase arrest by suppressing cyclinB1, cyclinD1, CDK2 and CDK4. Importantly, both genetic and pharmacological inhibition of EHMT2, through GADD45G knockdown or administration of the EHMT2 inhibitor BIX-01294, significantly reduced neointimal lesion formation in injury models. These findings collectively establish EHMT2 as a key epigenetic driver of vascular remodeling by repressing GADD45G and facilitating cell cycle progression, highlighting EHMT2 as a potential therapeutic target for vascular proliferative diseases. - Source: PubMed
Publication date: 2026/05/01
Wang ZelanZhao JunyongLuo WenjianSun NingMa XingyuZhong FangyuanWu BojiTang HengNing KeHe JingyuWang XuhongZhang KunZhang JihangLiu ChuanRen JunZhao YanQin Zhexue - Deoxynivalenol (DON), a prevalent food-borne mycotoxin, increasingly recognized as a potent driver in the progression of chronic liver disease to cirrhosis and hepatocellular carcinoma (HCC); however, its systematic role is unclear. This study aims to decode the pathogenic networks of DON through an integrated multi-omics and toxicological framework. - Source: PubMed
Publication date: 2026/04/08
Fu YunfengYang SichengPan YatingYan RunweiDu FanZhou Xiaodong - Hematopoietic stem cells (HSCs) self-renew and differentiate into all blood cells maintaining the hematopoietic system. Age-related HSC dysfunction impacts all of hematopoiesis, with DNA methylation alterations in aged HSCs contributing to altered function. Growth Arrest and DNA Damage-inducible proteins (Gadd45a, Gadd45b, and Gadd45g) are expressed in HSC activation, and Gadd45b has been reported to induce DNA demethylation. Thus, we explored the relationship between Gadd45b, DNA methylation and age-related HSC changes. WGBS on HSCs from GADD45B knockout mice demonstrated young knockout HSCs have increased DNA methylation, with both unique and overlapping methylation changes compared to aged wild-type HSCs without reflecting aging transcriptional changes. Peripheral blood and bone marrow analysis, competitive transplants, and single-cell culture analyses showed no significant loss of functional potential in the aberrantly methylated GADD45B knockout HSCs. We concluded these altered methylation sites don't alter HSC potential. We generated a searchable HSC DNA methylation database incorporating available datasets and present a truncated list of methylation sites associated with changes in HSC function for prioritization to target for resetting the age-associated loss of HSC potential. - Source: PubMed
Kuribayashi WakakoTanaka-Yano MayuriPark BongsooYanai HagaiTekin-Turhan FerdaBeerman Isabel - The liver is a primary target for recombinant adeno-associated viral (rAAV) vectors, yet the influence of serotype, sex, and liver zonation on transduction and transcriptomic changes remains incompletely understood. This proof-of-concept study employs spatial transcriptomics alongside single-nucleus RNA sequencing to map the spatial distribution and impacts of rAAV2- and rAAV9-CMV-EGFP vectors in male and female mouse livers. Spatial transcriptomics provided precise transgene mapping and highlighted that CMV-EGFP rAAV vectors deregulate hepatocellular lipid metabolism, the circadian clock, and the immune/stress response with sex specific differences. Lipid metabolism genes (Elovl3, Chka, Irs2, Ppard), were consistently deregulated across all zones of the liver lobule in male and female rAAV2- and rAAV9-CMV-EGFP-treated mice, while Srebf1, Tlcd4, Cpt2, and Acot1 exhibited sex-specific patterns. Circadian clock modulators (Dbp, Tef, Arntl, Nfil3, Nr1d1/Nr1d2) were altered independently of zonation. The study found sex-specific downregulation of immune and stress-response genes and pathways, including Gadd45g and hypoxia pathways. TGF-β and EGFR pathways were upregulated sex-independently. Spatial transcriptomics further enabled examination of transgene and rAAV entry factor co-expression, identifying known and novel factors like Rpsa, Dpp4, Sdc1, and solute carrier proteins, highlighting its role in supporting targeted screening. Our findings demonstrate spatial transcriptomics as a powerful tool in gene therapy research and reveal novel rAAV vector effects on liver biology. - Source: PubMed
Publication date: 2026/03/11
Amberg BettinaKöchl FabianKumpesa NadinePrasad MeganaBochner FilipHernández-Obiols MarOtteneder Michael BStalder LucasShaffo FrancesNowrouzi AliMarkusic DavidHaegel HélèneXicluna RebeccaSultan MarcJacobsen BjörnRottenberg SvenValdeolivas AlbertoSchwalie Petra CHahn Kerstin - Lung cancer is a leading cause of cancer-related mortality, with current therapies limited by drug resistance and immunosuppressive tumor microenvironment (TME). Cuproptosis offers new therapeutic prospects, but effective induction and targeted delivery remain challenging. Herein, we developed xanthohumol (XN)-coordinated copper oxide/hyaluronic acid (XN@CuO/HA) nanobipyramids as a novel cuproptosis inducer for non-small cell lung cancer (NSCLC) therapy. XN@CuO/HA exhibited good colloidal stability, and potent antitumor activity by inducing mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, and cuproptosis. Mechanistically, transcriptomic and functional analyses identified the FOXO1-GADD45G axis as a critical mediator of XN@CuO/HA-induced cuproptosis. , XN@CuO/HA significantly suppressed LLC xenograft growth in C57BL/6 mice with excellent biosafety. Moreover, it remodeled the immunosuppressive TME by enhancing CD8 T/NK1.1 cell infiltration and reducing MDSCs, synergizing with anti-PD-1 antibody to achieve superior antitumor efficacy. Collectively, our findings highlight XN@CuO/HA as a safe and effective nano-therapeutic that induces FOXO1-GADD45G-mediated cuproptosis and potentiates immunotherapy, providing a promising combinatorial strategy for NSCLC treatment. - Source: PubMed
Publication date: 2026/02/25
Jiang RuiyangHuang XiangmingOuyang YiranLuo BichongWan HongYangShou FangyangWu XiahuiFan JuntingZhang JingyuanSun DongdongXu ChangliangFang Zhijun