Ask about this productRelated genes to: ALKBH8 antibody
- Gene:
- ALKBH8 NIH gene
- Name:
- alkB homolog 8, tRNA methyltransferase
- Previous symbol:
- -
- Synonyms:
- MGC10235, TRM9, TRMT9A
- Chromosome:
- 11q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 2006-02-09
- Date modifiied:
- 2017-12-01
Related products to: ALKBH8 antibody
Related articles to: ALKBH8 antibody
- The human gene family comprises nine Fe/α-ketoglutarate-dependent dioxygenases that catalyze the oxidative demethylation of DNA, RNA, and proteins, thereby influencing key cellular processes. Consequently, dysregulation of these enzymes has been implicated in various human diseases, particularly cancer. Although the transcriptomic profiles of certain members (e.g., , ) have been characterized, a comprehensive analysis of the entire family remains unclear. In the present study, we investigated the alternative splice variants of the genes through direct RNA sequencing across cancerous and non-cancerous cell lines. Novel splicing events were validated by NGS, while RT-qPCR was employed to assess transcript abundance and expression patterns. Additionally, in silico analysis was performed to predict the coding potential of the detected transcripts. Results: Bioinformatics analysis revealed previously uncharacterized alternative transcripts for the human gene family members. Expression profiling demonstrated distinct expression patterns between cancerous and non-malignant cells, suggesting a potential role of these demethylases in tumor biology. The investigation of their coding capacity revealed that most of the newly detected transcripts were predicted to encode protein isoforms, highlighting the structural and predicted coding potential of the ALKBH family. Conclusions: Our findings provide the first comprehensive overview of the transcriptional diversity within the human gene family. These results enhance our understanding of the demethylation mechanisms and their dysregulation in cancer. - Source: PubMed
Publication date: 2026/02/26
Athanasopoulou KonstantinaMichalopoulou Vasiliki-IoannaTsiakanikas PanagiotisScorilas AndreasAdamopoulos Panagiotis G - encodes a β-tubulin isotype essential for neuronal proliferation, migration, and organization during brain development. Pathogenic heterozygous variants in have been associated with a range of neurodevelopmental disorders, with phenotypes including polymicrogyria and corpus callosum abnormalities. However, the phenotypic spectrum remains heterogeneous, likely influenced by variant-specific effects on microtubule formation and stability, an area that warrants further investigation. Homozygous variants are exceedingly rare, with one family reported to date. We describe five individuals in four families with rare variants. Four variant alleles are described, including a previously reported missense variant p.(G98R), with potential phenotypic expansion including panhypopituitarism, a previously reported missense variant, p.(I202T) demonstrating phenotypic heterogeneity between individuals, a missense variant, p.(Q15K) at a polyamination site critical for microtubule stability, and a novel homozygous missense variant located within a region of absence of heterozygosity in two siblings from consanguineous parents p.(V49I). Both individuals also have a pathogenic homozygous truncating variant in p.(R559Afs*56), representing a rare dual molecular diagnosis driving clinical features reflective of contributions from both genes. These cases expand the known clinical spectrum of -related tubulinopathies, illustrate intragenic phenotypic heterogeneity, including with recurrent variants and provide novel insights into potential mechanisms of disease, such as effects at polyamination sites and rare recessive inheritance, underscoring the need for nuanced genotype-phenotype interpretation in both diagnostic and counseling contexts. - Source: PubMed
Publication date: 2025/12/29
Beheshti Shaghayegh TJolly AngadSaad Ahmed KDu HaoweiWesterfield Lauren EMunderloh ChloeKalra DivyaWu YifanChen YiGingras Marie-ClaudeJhangiani Shalini NYilmaz SarenurZaki Maha SCalame Daniel GPehlivan DavutGibbs Richard ALewis Richard ALupski James RPosey Jennifer E - Reprogramming gene expression at the translational level drives intestinal tumorigenesis. Codon decoding during translation elongation relies on tRNA modifications, while their pathological relevance in colorectal cancer remains to be elucidated. Here, we show that AlkB homolog 8 (ALKBH8), a uridine 34 (U34) tRNA methyltransferase, is a direct target of Wnt/β-catenin and is upregulated in colorectal cancer. Genetic ablation of ALKBH8 inhibits the development of intestinal tumors in Apc, azoxymethane/dextran sulfate sodium (AOM/DSS), and xenograft models. Loss of ALKBH8 induces ribosome pausing at adenine-ending codons, impairing the translation elongation of mRNAs enriched with these codons. Specifically, ALKBH8 regulates the translation of KRAS proto-oncogene in a codon-dependent manner. Rescue experiments demonstrate that the methyltransferase activity of ALKBH8 is required for its translation-promoting function. Together, our findings reveal ALKBH8-dependent mRNA translation as a critical mediator of intestinal tumorigenesis, underscoring its potential as a promising target for colorectal cancer therapy. - Source: PubMed
Publication date: 2025/10/13
Qian YuWu CanlanWei SaisaiYan SujunPeng JunxuanYu LeiGao YunyiHou JingyuYu WentaoChen ZhanghuiZhang JunGao Xiangwei - Inhibitors of the protein kinase WEE1 have emerged as promising agents for cancer therapy. In this study, we uncover synergistic interactions between WEE1 small-molecule inhibitors and defects in mRNA translation, mediated by activation of the integrated stress response (ISR) through the kinase GCN2. Using a pooled CRISPRi screen, we identify GSPT1 and ALKBH8 as factors whose depletion confer hypersensitivity to the WEE1 inhibitor, AZD1775. We demonstrate that this synergy depends on ISR activation, which is induced by the off-target activity of WEE1 inhibitors. Furthermore, PROTAC-based WEE1 inhibitors and molecular glues show reduced or no ISR activation, suggesting potential strategies to minimise off-target toxicity. Our findings reveal that certain WEE1 inhibitors elicit dual toxicity via ISR activation and genotoxic stress, with ISR activation being independent of WEE1 itself or cell-cycle status. This dual mechanism highlights opportunities for combination therapies, such as pairing WEE1 inhibitors with agents targeting the mRNA translation machinery. This study also underscores the need for more precise WEE1 targeting strategies to mitigate off-target effects, with implications for optimising the therapeutic potential of WEE1 inhibitors. - Source: PubMed
Publication date: 2025/10/09
Wilson Jordan C JZhu JiaYiVinciauskaite VanesaLloyd Eloise GLam SimonHart AlexandraGoh Chen GangBou-Dagher FadiaRazumkov HlibKobel LenaKontarakis ZachariasFielden JohnSchlapansky Moritz FLoizou Joanna IVillunger AndreasCorn Jacob EBiffi GiuliaMasson Glenn RMarciniak Stefan JBader Aldo SJackson Stephen P - Although colorectal cancer is the second leading cause of cancer-related mortality in the United States, there has been limited progress in recent years in identifying new therapeutic options. However, cancer cells have been shown to be sensitive to ferroptosis, an iron-dependent lipid peroxide-induced form of cell death. In this issue of Cancer Research, DeAngelo and colleagues aimed to better understand the mechanisms underlying ferroptosis in colorectal cancer. However, using the ferroptosis-inducing small molecule RAS-selective lethal 3 (RSL3), they observed effects on colorectal cancer cells independent of RSL3's presumed target, glutathione peroxidase 4. Investigating further, they found that RSL3 inhibits multiple antioxidant proteins in the peroxidase and selenoprotein families to more broadly affect reactive oxygen species and lipid peroxidation than previously assumed. Loss of ALKBH8, a tRNA methyltransferase responsible for modifying the selenocysteine-specific tRNA, broadly decreased selenoprotein activity and induced ferroptosis in colorectal cancer. This work identifies the selenoproteome as a therapeutic target in colorectal cancer via induction of reactive oxygen species, lipid peroxidation, and ferroptosis and adds to a growing body of literature on the potential utility of pro-oxidant mechanisms in cancer therapy. See related article by DeAngelo et al., p. 2788. - Source: PubMed
Short Sarah P