Ask about this productRelated genes to: ALKBH3 Blocking Peptide
- Gene:
- ALKBH3 NIH gene
- Name:
- alkB homolog 3, alpha-ketoglutaratedependent dioxygenase
- Previous symbol:
- -
- Synonyms:
- DEPC-1
- Chromosome:
- 11p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 2006-02-09
- Date modifiied:
- 2018-05-03
Related products to: ALKBH3 Blocking Peptide
Related articles to: ALKBH3 Blocking Peptide
- Triple-negative breast cancer (TNBC) exhibits marked molecular heterogeneity, posing ongoing therapeutic challenges. Metabolic reprogramming, particularly through the Warburg effect, offers a promising therapeutic target for TNBC treatment. Data mining and machine learning identified (+)-miliusol as a promising candidate. Its direct target, eukaryotic initiation factor 3D (EIF3D), was validated through mass spectrometry-coupled cellular thermal shift assay (MS-CETSA), a biotinylated probe, and a proteolysis-targeting chimera (PROTAC) approach. EIF3D, an emerging oncoprotein and atypical translation initiation regulator, promotes tumor survival by selectively modulating protein synthesis. (+)-Miliusol demonstrates potent anti-proliferative and anti-migratory activity against TNBC in both and . Integrated proteomic and transcriptomic analyses revealed that (+)-miliusol suppresses TNBC progression through EIF3D-mediated translational regulation. Mechanistically, it disrupts the EIF3D-AlkB homolog 5 (ALKBH5)-glucose transporter type 4 (GLUT4) axis, EIF3D-HIF1 signaling, and the EIF3D-RuvB like AAA ATPase 1 (RUVBL1)--catenin pathway, thereby inhibiting glycolysis and metastasis while inducing ER stress-dependent apoptosis caspase-12 and JNK activation. Additionally, (+)-miliusol blocks EIF3D-HIF1 and EIF3D-ALKBH3 interactions, impairing ATAD2/PAK1-regulated Warburg-effect networks and triggering autophagy-associated cell death. (+)-Miliusol induces TNBC cell death by selectively suppressing translation of critical glycolytic and metastatic regulators. These findings establish EIF3D-mediated translational control as a promising therapeutic avenue for TNBC treatment. - Source: PubMed
Publication date: 2026/03/16
Zhang JinJia LinChen XiyaWu YanSun XiaohanZou LingCheng XiaolingHuang JingnanZhou HongchaoDai LingyunZhou LeHe ZhendanLiu BoHao YueYao Dahong - The AlkB homolog (ALKBH) family of Fe(II)/α-ketoglutarate-dependent dioxygenases mediates nucleic acid demethylation, thereby governing RNA metabolism and genomic stability. Despite their pivotal roles in epitranscriptomic regulation across vertebrates, the evolutionary dynamics and functional significance of ALKBH proteins in bivalve mollusks remain largely unexplored. Here, we present a comprehensive phylogenomic analysis of 210 ALKBH genes identified across 35 bivalve species. Our analyses reveal a distinct evolutionary trajectory characterized by the lineage-specific loss of ALKBH4 and the restricted distribution of ALKBH5 to the Mytilidae family, contrasting sharply with vertebrate repertoires. Using the noble scallop (Chlamys nobilis) and Pacific oyster (Crassostrea gigas) as model systems, we demonstrate that ALKBH genes exhibit conserved spatiotemporal expression patterns, with pronounced enrichment in gonadal tissues and during metamorphic transitions, implicating these enzymes in gametogenesis and larval development. Furthermore, comparative thermal stress experiments reveal divergent transcriptional plasticity: the subtropical scallop C. nobilis mounts rapid, transient induction of ALKBH1/2/6 under heat shock, whereas the eurythermal oyster C. gigas maintains sustained ALKBH3 expression, potentially underpinning its superior thermal tolerance. Conversely, cold stress elicits bimodal regulation in C. nobilis, with ALKBH1/2 upregulation contrasting with ALKBH6/7/8 suppression. These findings illuminate the functional diversification of bivalve ALKBH genes and their potential utility as molecular biomarkers for assessing developmental competence and thermal resilience in shellfish aquaculture. - Source: PubMed
Publication date: 2026/06/16
Xiong DalinLi YifanHu HaixinHe QiqiSu HailongLiao WeiminXu TianyiXu ChangpingZhang HongkuanZheng Huaiping - AlkB-family Fe(II)/2-oxoglutarate-dependent dioxygenases repair alkylated nucleic acid lesions through oxidative dealkylation and play important roles in genome maintenance. 1-Methyl-2'-deoxyadenosine (1mA) and 3-methyl-2'-deoxycytidine (3mC) are well-established substrates of AlkB, ALKBH2, and ALKBH3. Although these enzymes have been extensively studied, the influence of proton concentration (pH) on their catalytic behavior and strand preference remains poorly defined. Here, we systematically examined how pH modulates the activity of the prototypical bacterial AlkB and the human homologues ALKBH2 and ALKBH3 using defined DNA substrates in both single-stranded (ssDNA) and double-stranded (dsDNA) contexts containing 1mA and 3mC lesions. Across a broad pH range, all three enzymes mainly exhibit bell-shaped activity profiles with distinct optima. The prevailing view in the field is that AlkB preferentially repairs these lesions in ssDNA, ALKBH2 favors dsDNA, and ALKBH3 prefers ssDNA. However, our results demonstrate that pH influences the catalytic efficiency and strand utilization in a substrate- and enzyme-dependent manner. AlkB maintains a consistent ssDNA preference for 3mC but exhibits variable strand preference for 1mA at different pH values. ALKBH2 retains a strong dsDNA preference for 1mA across all conditions but shows a clear pH-dependent strand switch for 3mC, favoring ssDNA under acidic conditions and preferring dsDNA at neutral to alkaline pH conditions. In contrast, ALKBH3 consistently favors ssDNA for 3mC but exhibits pH-dependent strand preference for 1mA. Our results show that the reported strand preferences largely hold at pH 7.0-8.0 but are not complete, as strand utilization and pH optima vary by enzyme and substrate. The observations demonstrate that proton availability strongly influences AlkB-family catalysis and is an important factor in how these enzymes process damaged DNA. These findings may also aid the optimization of AlkB-based protein engineering and sequencing technologies. - Source: PubMed
Publication date: 2026/06/08
Howarth Samuel DMylie Quentin JBoateng-Boakye EvansFalkowski VincentOliver Mella AmbarFermin RafaelPeng ZhiyuanBush XinChen Yi-TzaiMa JianCho BongsupLi Deyu - Liver cancer remains one of the leading causes of cancer-related mortality worldwide, with its progression driven by uncontrolled cell proliferation and evasion of apoptosis. N1-methyladenosine (mA) is a prevalent RNA modification implicated in cancer progression, yet its role in liver cancer remains unclear. Here, we report a significant reduction in mA levels in liver cancer tissues, which contributes to apoptosis evasion in liver cancer cells. We demonstrate that ALKBH3, an mA demethylase, regulates apoptosis by modulating BIRC2 expression. Specifically, ALKBH3 depletion destabilizes BIRC2 mRNA by promoting its degradation, facilitated by mA modifications at positions A98/99/100 in the 5'-UTR of BIRC2. These modifications enhance the interaction between BIRC2 mRNA and the YTHDF3/CNOT1-XRN2 complex, thereby driving mRNA degradation. In vitro, in vivo, and clinical analyses validate the critical role of the mA/BIRC2 axis in regulating apoptosis and tumor progression in liver cancer. Our findings underscore the therapeutic potential of targeting the mA/BIRC2 axis to overcome apoptosis resistance in liver cancer, offering new avenues for intervention in this malignancy. - Source: PubMed
Publication date: 2026/04/16
Wu YingminZhang ShenjieZhang ShilongLu JieyuYang YuntaoZeng ZhiruiLei ShanMi RuiZhang YeweiGe LichenChen TengxiangLi Haiyang - : Metabolic dysfunction-associated steatotic liver disease (MASLD) is a globally prevalent condition with a complex pathogenesis. While both m6A RNA methylation regulators and gut microbiota have been independently implicated in MASLD, their potential causal interplay remains unexplored. This study aimed to investigate the causal relationships among m6A regulatory genes, gut microbiota, and MASLD, and to assess the mediating role of gut microbiota. : We performed a two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) data. Genetic instruments for m6A regulators were derived from blood expression quantitative trait loci (eQTL) data. Gut microbiota and MASLD data were obtained from large-scale metagenomic and disease GWAS, respectively. The inverse-variance weighted method was the primary analysis, supplemented by sensitivity and mediation analyses to evaluate potential mediating pathways. : Genetically predicted levels of four m6A regulators showed significant causal associations with MASLD risk: ALKBH3 increased risk (OR = 1.17), whereas ALKBH5 (OR = 0.89), CBLL1 (OR = 0.76), and RBM15B (OR = 0.83) were protective. Nineteen gut microbial taxa were causally linked to MASLD. Among these, seven taxa were influenced by the four identified m6A genes. Although no mediation effects reached strict statistical significance, the pathway from ALKBH5 to MASLD via Parabacteroides abundance showed a suggestive indirect effect accounting for 21.9% of the total effect ( = 0.068). Given the limited statistical power of mediation analyses in MR settings, this observation should be interpreted with caution and requires validation in larger, well-powered studies. : This MR study provides genetic evidence supporting causal roles of specific m6A regulators in MASLD and suggests that gut microbiota may partially mediate these relationships. The findings highlight a potential "m6A-gut microbiota-liver" axis in MASLD pathogenesis. - Source: PubMed
Publication date: 2026/03/11
Qiu DongmeiSuo LiweiWei TaoLu ZhenweiWeng QixinXiao JianxingWang XinchiXu QinyuWu Jingtong