Affinage

ALKBH3

Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 · UniProt Q96Q83

Length
286 aa
Mass
33.4 kDa
Annotated
2026-06-09
41 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA, functioning both as an alkylation-damage repair enzyme and as an epitranscriptomic eraser that controls mRNA fate (PMID:22055184, PMID:30541109, PMID:26967262). In its DNA-repair role, ALKBH3 acts within the ASCC complex: the ASCC3 3'-5' helicase generates the single-stranded substrate ALKBH3 prefers, and loss of either protein elevates 3-methylcytosine and triggers DNA-damage signaling and reduced proliferation (PMID:22055184). The complex is targeted to nuclear alkylation sites through the ASCC2 CUE domain, which reads K63-linked polyubiquitin chains (PMID:34971705), and ALKBH3 repair of methyl adducts on 3'-tailed DNA is further stimulated by direct interaction with the recombination factor RAD51C (PMID:31642493). Crystal structures of substrate-crosslinked ALKBH3 show that the enzyme grips single-stranded substrate via two beta-hairpins and an alpha2 helix and everts the methylated base, with active-site residue Thr133 dictating m1A/m3C selectivity (its substitution by the corresponding FTO/ALKBH5 residue switches selectivity toward m6A) and Asp194 and Tyr143 contributing to substrate recognition and base eversion (PMID:38158383, PMID:38256217). As an RNA demethylase, ALKBH3 strips m1A from numerous target mRNAs to govern their stability and translation: by erasing m1A it either prevents reader-driven decay—removing marks recognized by YTHDF2/PAN2-PAN3 or, conversely, by the stabilizing reader YTHDF1—or otherwise alters transcript half-life, thereby controlling targets such as CSF-1, Aurora A, METTL3, ALDOA, HK2, VEGFA, PINK1, ZBED6, and Mmp15 (PMID:30342176, PMID:35277482, PMID:38118002, PMID:40019372, PMID:40654364, PMID:40493193, PMID:41816968, PMID:41816893, PMID:39004750). Through this mRNA-regulatory activity ALKBH3 influences a broad range of processes including cancer cell invasion and glycolysis, ciliogenesis, hippocampal neurogenesis, mitophagy, neovascularization, and cell-survival decisions (PMID:30342176, PMID:35277482, PMID:39004750, PMID:40493193, PMID:41816968). ALKBH3 also demethylates tRNA, sensitizing it to angiogenin cleavage and generating tRNA-derived small RNAs that support ribosome assembly and suppress apoptosis (PMID:30541109).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2011 High

    Established that ALKBH3 is not a stand-alone repair enzyme but operates within the ASCC complex, where the ASCC3 helicase supplies the single-stranded DNA substrate it acts upon.

    Evidence Complex purification, in vitro helicase assay, and siRNA epistasis with DNA-damage readouts in human cells

    PMID:22055184

    Open questions at the time
    • Did not resolve how the complex is recruited to damage sites
    • Substrate generation linked to ssDNA but RNA substrates not addressed
  2. 2015 Medium

    Showed ALKBH3 occupies transcription-associated chromatin (paused Pol II, enhancers, active promoters), raising the possibility of a chromatin/transcription-linked role beyond bulk DNA repair.

    Evidence Endogenous ALKBH3 ChIP-seq with expression microarray after depletion in prostate cancer cells

    PMID:26221185

    Open questions at the time
    • Depletion did not alter transcription of bound genes, leaving the functional consequence of binding unresolved
    • Mechanism linking ALKBH3 chromatin occupancy to inflammatory gene upregulation unknown
  3. 2016 High

    Provided quantitative kinetic tools and lesion-specificity data, confirming ALKBH3 acts on m1A with measurable kinetics and on specific N3-alkyl thymidine lesions while sparing others.

    Evidence Fluorogenic m1A probe with Km/kcat and live-cell imaging; transcription-bypass lesion-repair assays for N3-alkyl lesions

    PMID:26930515 PMID:26967262

    Open questions at the time
    • In vitro reconstitution for ALKBH3 on N3-EtdT specifically not performed
    • Cellular substrate scope incompletely defined
  4. 2018 Medium

    Opened the epitranscriptomic role by showing ALKBH3 m1A-demethylates a specific mRNA (CSF-1) to extend its half-life and drive cancer invasiveness, establishing mRNA stability as an ALKBH3 output.

    Evidence ALKBH3 overexpression/knockdown, m1A mapping, mRNA half-life and invasion assays in breast/ovarian cancer cells

    PMID:30342176

    Open questions at the time
    • The reader interpreting m1A on CSF-1 mRNA was not identified (YTHDF2 excluded)
    • No in vitro reconstitution of the demethylation event
  5. 2019 High

    Defined ALKBH3 as an m1A/m3C eraser on tRNA and linked its activity to tRNA-derived small RNA production, ribosome assembly, and apoptosis resistance, expanding substrate scope beyond DNA and mRNA.

    Evidence In vitro demethylation, tDR profiling, ribosome assembly and apoptosis assays, xenograft

    PMID:30541109

    Open questions at the time
    • Specific tRNA species and sites incompletely defined
    • Coupling between demethylation and angiogenin cleavage not structurally resolved
  6. 2019 Medium

    Identified RAD51C as a direct ALKBH3 partner that stimulates repair of methyl adducts on 3'-tailed DNA, connecting ALKBH3 alkylation repair to recombination machinery.

    Evidence Reciprocal co-IP/pulldown, in vitro demethylation on 3'-tailed substrates, cellular alkylation-resistance assay

    PMID:31642493

    Open questions at the time
    • Single lab; structural basis of interaction unknown
    • Relationship to the ASCC complex not addressed
  7. 2019 Medium

    Demonstrated that ALKBH3 (with ALKBH2) can oxidize carbon-bound 5-methylcytosine to 5hmC/5fC/5caC in vitro, broadening its potential chemistry beyond N-demethylation.

    Evidence In vitro enzymatic assay with purified protein, mass spectrometry, computational docking

    PMID:31114894

    Open questions at the time
    • No cellular validation that this activity occurs in vivo
    • Biological significance of 5mC oxidation by ALKBH3 unknown
  8. 2021 Medium

    Resolved how the ASCC-ALKBH3 complex is recruited to damage and how it accesses mRNA substrates, linking K63-ubiquitin recognition and ribosome disassembly to demethylation.

    Evidence ASCC2 CUE-domain structure/mutagenesis with nuclear recruitment assay; ASCC3 KO cells with MS quantitation of mRNA m1A/m3C and P-body imaging

    PMID:34217309 PMID:34971705

    Open questions at the time
    • Direct demonstration that ASCC3-driven ribosome disassembly is required for ALKBH3 catalysis not shown
    • Single labs for each mechanism
  9. 2022 High

    Provided in vivo proof that ALKBH3 catalytic m1A demethylation of a target mRNA (Aurora A) controls a developmental process (ciliogenesis), as a catalytically dead mutant failed to rescue zebrafish defects.

    Evidence mRNA decay/translation assays, catalytic mutant rescue, zebrafish morpholino phenotype rescue

    PMID:35277482

    Open questions at the time
    • Reader machinery for Aurora A m1A not defined
    • Generality across cilia-related transcripts not established
  10. 2024 High

    Delivered the structural and kinetic basis of ALKBH3 substrate selectivity, showing Thr133 governs m1A/m3C versus m6A choice and identifying residues for ssDNA binding and base eversion.

    Evidence X-ray crystallography of substrate-crosslinked complexes plus mutagenesis; stopped-flow/CD kinetics defining binding, eversion, anchoring steps

    PMID:38158383 PMID:38256217

    Open questions at the time
    • Structures used DNA oligo substrates; RNA-bound conformation not solved
    • How active-site selectivity maps onto tRNA/mRNA targets in vivo unresolved
  11. 2024 Medium

    Showed ALKBH3 m1A erasure tunes mRNA fate through specific readers — preventing YTHDF1-mediated stabilization (SP100A) — coupling the eraser to defined reader-decay logic, and identified a regulatory input via PUS7 pseudouridylation of ALKBH3 mRNA controlling its own translation.

    Evidence Multiomics with rescue and reader (YTHDF1) interaction assays; locus-specific pseudouridine mapping with polysome profiling and xenograft

    PMID:38118002 PMID:39175405

    Open questions at the time
    • Reader assignment varies by transcript; rules for reader choice unclear
    • Upstream control of ALKBH3 expression in physiological contexts incompletely mapped
  12. 2025 Medium

    Expanded the m1A-eraser regulon to metabolic and signaling targets — METTL3, HK2/VEGFA, ALDOA — establishing ALKBH3 as a driver of glycolysis, neovascularization, fibrosis, and chemoresistance via YTHDF2/PAN2-PAN3-dependent decay and a lactylation feedback loop.

    Evidence Site-specific m1A editing (dm1ACRISPR), knockdown/overexpression with reader/degradation-complex interaction assays, ChIP for histone lactylation, inhibitor and in vivo models

    PMID:40019372 PMID:40493193 PMID:40654364

    Open questions at the time
    • Each pathway from a single lab
    • Whether one demethylase coordinates these target sets simultaneously not addressed
  13. 2026 Medium

    Extended ALKBH3 target regulation to neuronal and cardiac homeostasis — PINK1-dependent mitophagy in Alzheimer's models and a ZBED6-STAT1-AIM2 axis controlling cardiomyocyte PANoptosis — implicating it in degenerative and ischemic disease.

    Evidence m1A epitranscriptomics, in vivo 5xFAD and I/R models, co-IP, ChIP, luciferase reporter, stability/translation assays

    PMID:41816893 PMID:41816968

    Open questions at the time
    • Direct mapping of m1A demethylation events partly inferential
    • Single-lab disease models awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ALKBH3 partitions among its DNA-repair, tRNA, and mRNA substrate pools in a given cell, and what determines which reader and outcome a demethylated transcript receives.
  • No unified model of substrate selection across DNA vs RNA in vivo
  • Rules dictating reader assignment (YTHDF1 vs YTHDF2/PAN2-PAN3) per transcript unknown
  • Regulation balancing nuclear repair vs cytoplasmic mRNA roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 8 GO:0140097 catalytic activity, acting on DNA 4 GO:0003677 DNA binding 3 GO:0003723 RNA binding 3 GO:0016491 oxidoreductase activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-8953854 Metabolism of RNA 5 R-HSA-73894 DNA Repair 4 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 1
Partners
ASCC2ASCC3RAD51C
Complex memberships
ASCC complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 ALKBH3 forms a complex with the Activating Signal Cointegrator Complex (ASCC), and ASCC3 (the largest subunit) encodes a 3'-5' DNA helicase whose activity generates single-stranded DNA upon which ALKBH3 preferentially performs dealkylation. Loss of either ALKBH3 or ASCC3 leads to increased 3-methylcytosine levels, reduced cell proliferation, and pH2A.X/53BP1 foci formation. Protein complex purification, co-immunoprecipitation, helicase activity assay, siRNA knockdown with DNA damage readouts (pH2A.X, 53BP1 foci), cell proliferation assay Molecular cell High 22055184
2019 ALKBH3 is a 1-methyladenosine (m1A) and 3-methylcytidine (m3C) demethylase of tRNA. ALKBH3-demethylated tRNA is more sensitive to angiogenin (ANG) cleavage, generating tRNA-derived small RNAs (tDRs) around anticodon regions that strengthen ribosome assembly and prevent cytochrome c-triggered apoptosis. In vitro demethylation assay, tDR profiling, ribosome assembly assay, apoptosis assay (cytochrome c), siRNA knockdown, xenograft tumor model Nucleic acids research High 30541109
2018 ALKBH3-mediated m1A demethylation of CSF-1 mRNA increases CSF-1 mRNA stability (half-life) in breast and ovarian cancer cells, promoting cancer cell invasiveness. The m1A site is mapped to the 5'UTR near the translation initiation site, and YTHDF2 (an m6A reader) is not the reader of m1A-containing CSF-1 mRNA. ALKBH3 overexpression/knockdown, mRNA stability assay (half-life measurement), m1A mapping, invasion assay, YTHDF2 interaction test Biochimica et biophysica acta. Gene regulatory mechanisms Medium 30342176
2019 ALKBH2 and ALKBH3 (and E. coli AlkB) can oxidize 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine in vitro, demonstrating capacity to oxidize a methyl group attached to carbon rather than nitrogen. In vitro enzymatic assay with purified proteins, mass spectrometry detection of oxidized products, computational docking Nucleic acids research Medium 31114894
2022 ALKBH3 removes m1A from Aurora A mRNA, stabilizing it and promoting its translation; depletion of ALKBH3 enhances Aurora A mRNA decay and inhibits its translation, leading to inhibition of ciliogenesis. The catalytically inactive ALKBH3 mutant cannot rescue ciliary defects in alkbh3 morphant zebrafish, confirming the demethylation activity is required. ALKBH3 knockdown/overexpression, Aurora A mRNA stability and translation assays, catalytic mutant rescue, zebrafish alkbh3 morpholino knockdown with phenotypic rescue experiments Cell discovery High 35277482
2019 ALKBH3 directly interacts with human RAD51 paralogue RAD51C via protein-protein interaction, and RAD51C-ALKBH3 interaction stimulates ALKBH3-mediated repair of methyl-adducts within 3'-tailed DNA substrates; disruption of this interaction impairs ALKBH3 function both in vitro and in vivo. Co-immunoprecipitation, pulldown assay, in vitro demethylation assay with 3'-tailed DNA substrates, cellular alkylation damage resistance assay Nucleic acids research Medium 31642493
2021 ASCC3, the ALKBH3 binding partner, mediates P-body formation and promotes selective removal of chemically induced m1A and m3C from mRNA; ASCC3-deficient cells show delayed clearance of MMS-induced m1A and m3C from mRNA and impaired P-body formation, consistent with a model where ASCC3-mediated ribosome disassembly allows ALKBH3-dependent mRNA demethylation. Quantitative mass spectrometry of mRNA methylation, SILAC proteomics of mRNA-binding proteins, ASCC3 knockout cells, P-body imaging Journal of translational medicine Medium 34217309
2015 ALKBH3 binds to transcription-associated genomic locations including promoter-proximal paused RNA Pol II sites and enhancers in prostate cancer cells; it strongly binds to transcription initiation sites of a small number of highly active promoters characterized by high levels of Mediator, cohesin, and active histone marks. ALKBH3 depletion does not directly alter transcription of its target genes but induces upregulation of ALKBH3-non-bound inflammatory genes. ChIP-seq (endogenous ALKBH3), microarray gene expression after ALKBH3 depletion Genome medicine Medium 26221185
2016 A fluorogenic probe (MAQ) exploiting fluorescence quenching of 1-methyladenine enables direct measurement of ALKBH3 repair activity in vitro and in cells; the probe is specific for ALKBH3 over ALKBH2 and shows Km and kcat values equivalent to the native substrate. ALKBH3 activity was imaged and quantified in live cells by microscopy and flow cytometry. Fluorogenic substrate assay, enzyme kinetics (Km, kcat), specificity comparison with ALKBH2, live-cell imaging, flow cytometry Journal of the American Chemical Society High 26967262
2024 Crystal structures of ALKBH3 crosslinked to oligonucleotide substrates (obtained with a synthetic antibody chaperone) reveal that ALKBH3 uses two β-hairpins (β4-loop-β5 and β'-loop-β'') and an α2 helix for single-stranded substrate binding. Residue Thr133 in the active pocket is required for specific recognition of m1A and m3C; mutation of Thr133 to the corresponding FTO or ALKBH5 residue converts ALKBH3 substrate selectivity from m1A to m6A. Asp194 forms a bubble-like region also critical for substrate recognition. X-ray crystallography of ALKBH3-oligo crosslinked complexes, site-directed mutagenesis (Thr133, Asp194), in vitro demethylation assay with mutants Angewandte Chemie (International ed. in English) High 38158383
2024 Biochemical and mutagenesis analysis identifies Tyr143, Leu177, and His191 as key residues for ALKBH3 secondary structure and catalytic activity toward methylated single-stranded DNA. Tyr143 is critical for binding the flipped-out methylated base and stabilizing its everted conformation; Leu177 and His191 are required for secondary structure integrity. Stopped-flow fluorescence spectroscopy revealed a transient kinetic mechanism comprising substrate binding, base eversion, and anchoring steps. Site-directed mutagenesis, stopped-flow fluorescence spectroscopy, CD spectroscopy, in vitro activity assays International journal of molecular sciences Medium 38256217
2021 The ASCC2 CUE domain selectively binds K63-linked polyubiquitin chains (diubiquitin) by contacting both the distal and proximal ubiquitin, thereby localizing the ASCC-ALKBH3 repair complex to alkylation damage sites in the nucleus. Mutation of residues in the N-terminal portion of the ASCC2 α1 helix that contact the proximal ubiquitin decreases ASCC2 nuclear recruitment in response to DNA alkylation. Co-crystallography/structural analysis, mutagenesis of ASCC2 CUE domain, cellular ASCC2 recruitment assay upon DNA alkylation damage The Journal of biological chemistry Medium 34971705
2016 Alkbh3 (and Alkbh2), but not alkyladenine DNA glycosylase (Aag), can repair N3-ethylthymidine (N3-EtdT) in mammalian cells, as shown by transcription-based lesion bypass assays. Purified human Alkbh2 directly reverses N3-EtdT in vitro. N3-CMdT, O2-EtdT, O4-EtdT, and O4-CMdT are not repaired by Alkbh2 or Alkbh3. Site-specific lesion in non-replicative vectors, transcription bypass assay in mammalian cells, in vitro repair assay with purified Alkbh2 ACS chemical biology Medium 26930515
2024 ALKBH3-mediated m1A demethylation of SP100A mRNA prevents its recognition by YTHDF1 (an m1A reader that promotes RNA stability and translation), thereby reducing SP100A protein levels and attenuating formation of tumor-suppressive PML nuclear condensates. YTHDF1 is identified as a reader of m1A-methylated SP100A mRNA. Multiomics (m1A epitranscriptomics + proteomics), ALKBH3 knockdown with SP100A rescue, YTHDF1 interaction with m1A-containing mRNA, in vitro/in vivo functional assays Nucleic acids research Medium 38118002
2025 ALKBH3 demethylates m1A on METTL3 mRNA, preventing YTHDF2-dependent mRNA decay of METTL3 transcript and thereby increasing METTL3 protein levels. Elevated METTL3 then stabilizes COL1A1 and FN1 mRNAs via m6A modification, promoting pathological skin fibrosis (hypertrophic scars). m1A epitranscriptomics, ALKBH3 knockdown/overexpression, METTL3 rescue experiments, in vitro and in vivo fibrosis models, YTHDF2 interaction assay Advanced science Medium 40019372
2024 m1A demethylase Alkbh3 promotes neurogenesis by demethylating m1A on Mmp15 mRNA, improving its RNA stability and translational efficacy; depletion of Alkbh3 in neural stem cells decreases neuronal differentiation and proliferation while increasing gliogenesis, and reduces hippocampal neurogenesis and spatial memory in adult mice. Alkbh3 knockdown/overexpression in neural stem cells, Mmp15 mRNA stability and translation assay, m1A profiling, in vivo hippocampal neurogenesis and behavioral testing Cell & bioscience Medium 39004750
2025 ALKBH3 demethylates m1A on HK2 mRNA in retinal pigment epithelial cells, activating glycolysis and excess lactate production. This lactate promotes H3K18 histone lactylation, which binds the ALKBH3 promoter to amplify its transcription, establishing a positive feedback loop. ALKBH3 also directly demethylates VEGFA mRNA to promote choroidal neovascularization. dm1ACRISPR system for site-specific m1A demethylation, gene knockout mice, ChIP for histone lactylation at ALKBH3 promoter, m1A epitranscriptomics, ALKBH3 inhibitor (HUHS015), in vivo AMD model Proceedings of the National Academy of Sciences of the United States of America Medium 40493193
2025 ALKBH3-mediated m1A demethylation of ALDOA mRNA at the 3'UTR stabilizes ALDOA mRNA by preventing recruitment of the YTHDF2/PAN2-PAN3 complex that drives mRNA degradation; this stabilization potentiates glycolysis and doxorubicin resistance in triple-negative breast cancer cells. ALKBH3 knockdown/overexpression, m1A site mapping in ALDOA 3'UTR, mRNA stability assay, YTHDF2/PAN2-PAN3 interaction assay, glycolysis metabolite measurement, in vivo xenograft Acta pharmaceutica Sinica. B Medium 40654364
2026 ALKBH3 removes m1A from PINK1 mRNA, promoting its stability and translation; elevated ALKBH3 in Alzheimer's disease models impairs PINK1-dependent mitophagy, leading to mitochondrial dysfunction and neuronal damage. Alkbh3 reduction decreases amyloid-β plaques and restores cognition in 5xFAD mice. m1A epitranscriptomics, Alkbh3 knockout/reduction in 5xFAD mice, PINK1 mRNA stability and translation assays, mitophagy and mitochondrial function assays, behavioral testing Advanced science Medium 41816968
2026 ALKBH3 demethylates m1A on ZBED6 mRNA, enhancing ZBED6 translation; ZBED6 then physically interacts with STAT1 (confirmed by co-immunoprecipitation and ChIP) and represses STAT1-driven AIM2 transcription, thereby suppressing PANoptosis (pyroptosis/apoptosis/necroptosis) in cardiomyocytes during ischemia/reperfusion injury. m1A epitranscriptomics, ALKBH3 overexpression/siRNA in cells and in vivo I/R model, co-immunoprecipitation (ZBED6-STAT1), ChIP, dual-luciferase reporter (AIM2 promoter), loss- and gain-of-function for ZBED6, STAT1, AIM2 Clinical and translational medicine Medium 41816893
2024 PUS7-dependent pseudouridylation of ALKBH3 mRNA at position U696 enhances its translation efficiency, thereby increasing ALKBH3 protein levels and suppressing gastric cancer progression. Locus-specific pseudouridine detection assay, polysome profiling, RT-qPCR, Western blotting, 3D colony formation assay, xenograft model Clinical and translational medicine Medium 39175405
2025 ALKBH3-mediated m1A demethylation of ATF4 mRNA increases ATF4 expression, which inhibits ferroptosis (by upregulating SLC7A11, GPX4, FTH1) and promotes AML cell survival; ALKBH3 knockdown promotes ferroptosis in KG-1 cells. ALKBH3 knockdown, ATF4 knockdown rescue experiments, ferroptosis markers (ROS, MDA, iron, SOD, GSH), flow cytometry, xenograft model Hematology Low 39803678

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs. Nucleic acids research 302 30541109
2011 DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation. Molecular cell 175 22055184
2018 Human ALKBH3-induced m1A demethylation increases the CSF-1 mRNA stability in breast and ovarian cancer cells. Biochimica et biophysica acta. Gene regulatory mechanisms 134 30342176
2024 Histone lactylation-boosted ALKBH3 potentiates tumor progression and diminished promyelocytic leukemia protein nuclear condensates by m1A demethylation of SP100A. Nucleic acids research 112 38118002
2011 ALKBH3, a human AlkB homologue, contributes to cell survival in human non-small-cell lung cancer. British journal of cancer 104 21285982
2012 PCA-1/ALKBH3 contributes to pancreatic cancer by supporting apoptotic resistance and angiogenesis. Cancer research 88 22826605
2012 ALKBH3 contributes to survival and angiogenesis of human urothelial carcinoma cells through NADPH oxidase and tweak/Fn14/VEGF signals. Clinical cancer research : an official journal of the American Association for Cancer Research 69 22850567
2019 DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro. Nucleic acids research 66 31114894
2022 ALKBH3-dependent m1A demethylation of Aurora A mRNA inhibits ciliogenesis. Cell discovery 44 35277482
2016 Fluorescence Monitoring of the Oxidative Repair of DNA Alkylation Damage by ALKBH3, a Prostate Cancer Marker. Journal of the American Chemical Society 41 26967262
2015 Clinical significance and therapeutic potential of prostate cancer antigen-1/ALKBH3 in human renal cell carcinoma. Oncology reports 33 26035443
2019 Human RAD51 paralogue RAD51C fosters repair of alkylated DNA by interacting with the ALKBH3 demethylase. Nucleic acids research 26 31642493
2024 PUS7-dependent pseudouridylation of ALKBH3 mRNA inhibits gastric cancer progression. Clinical and translational medicine 24 39175405
2024 The Molecular Basis of Human ALKBH3 Mediated RNA N1 -methyladenosine (m1 A) Demethylation. Angewandte Chemie (International ed. in English) 23 38158383
2017 CpG promoter methylation of the ALKBH3 alkylation repair gene in breast cancer. BMC cancer 23 28679371
2018 Indenone derivatives as inhibitor of human DNA dealkylation repair enzyme AlkBH3. Bioorganic & medicinal chemistry 21 30041948
2021 ALKBH3 partner ASCC3 mediates P-body formation and selective clearance of MMS-induced 1-methyladenosine and 3-methylcytosine from mRNA. Journal of translational medicine 20 34217309
2015 The oxidative demethylase ALKBH3 marks hyperactive gene promoters in human cancer cells. Genome medicine 20 26221185
2018 Novel Metabolically Stable PCA-1/ALKBH3 Inhibitor Has Potent Antiproliferative Effects on DU145 Cells In Vivo. Anticancer research 18 29277775
2016 Roles of Aag, Alkbh2, and Alkbh3 in the Repair of Carboxymethylated and Ethylated Thymidine Lesions. ACS chemical biology 16 26930515
2017 TP53 gene status is a critical determinant of phenotypes induced by ALKBH3 knockdown in non-small cell lung cancers. Biochemical and biophysical research communications 12 28479246
2025 ALKBH3-Mediated M1A Demethylation of METTL3 Endows Pathological Fibrosis:Interplay Between M1A and M6A RNA Methylation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 11 40019372
2024 m1A demethylase Alkbh3 regulates neurogenesis through m1A demethylation of Mmp15 mRNA. Cell & bioscience 11 39004750
2022 LncRNA ALKBH3-AS1 enhances ALKBH3 mRNA stability to promote hepatocellular carcinoma cell proliferation and invasion. Journal of cellular and molecular medicine 10 36098205
2020 ALKBH3 is dispensable in maintaining hematopoietic stem cells but forced ALKBH3 rectified the differentiation skewing of aged hematopoietic stem cells. Blood science (Baltimore, Md.) 10 35400026
2016 A real-time PCR-based quantitative assay for 3-methylcytosine demethylase activity of ALKBH3. Biochemistry and biophysics reports 9 28955855
2021 The ASCC2 CUE domain in the ALKBH3-ASCC DNA repair complex recognizes adjacent ubiquitins in K63-linked polyubiquitin. The Journal of biological chemistry 8 34971705
2021 Demethylation of m1A assisted degradation of the signal probe for rapid electrochemical detection of ALKBH3 activity with practical applications. Talanta 6 34942472
2025 Feedback regulation between histone lactylation and ALKBH3-mediated glycolysis regulates age-related macular degeneration pathology. Proceedings of the National Academy of Sciences of the United States of America 5 40493193
2025 ALKBH3-regulated m1A of ALDOA potentiates glycolysis and doxorubicin resistance of triple negative breast cancer cells. Acta pharmaceutica Sinica. B 5 40654364
2025 ALKBH3-mediated m1A demethylation promotes the malignant progression of acute myeloid leukemia by regulating ferroptosis through the upregulation of ATF4 expression. Hematology (Amsterdam, Netherlands) 4 39803678
2025 Site-Specific Mitochondrial RNA N1-Methyladenosine Demethylation via an Engineered MTS-PUF-ALKBH3 Fusion Protein. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 41144740
2025 Dual-Mode Detection of RNA Demethylation Protein ALKBH3 Using a Two-Legged DNA-Walker-Mediated BiOI/In2O3-Gated Organic Photoelectrochemical Transistor Biosensor. Small (Weinheim an der Bergstrasse, Germany) 2 40384259
2025 ALKBH3-AS1 drives SMAD3 stabilization via YTHDF2: Uncovering a pathogenic pathway for Th17 dysregulation in SLE. Pharmacological research 1 41086975
2024 The Role of Key Amino Acids of the Human Fe(II)/2OG-Dependent Dioxygenase ALKBH3 in Structural Dynamics and Repair Activity toward Methylated DNA. International journal of molecular sciences 1 38256217
2024 Synergistic combination effect of the PCA-1/ALKBH3 inhibitor HUHS015 on prostate cancer drugs in vitro and in vivo. Anti-cancer drugs 1 39259581
2024 Evaluation of ALKBH2 and ALKBH3 gene regulation in patients with adult T-cell leukemia/lymphoma. Virology journal 1 39633427
2021 Sequence Dependent Repair of 1,N6-Ethenoadenine by DNA Repair Enzymes ALKBH2, ALKBH3, and AlkB. Molecules (Basel, Switzerland) 1 34500720
2026 Histone modification-regulated LncRNA DLEU1 interacts with ASCC2/ALKBH3 complex to drive DNA repair, antioxidant homeostasis and glucose metabolism in gastric cancer. Biomarker research 0 41484982
2026 ALKBH3 suppresses ischemia/reperfusion-induced PANoptosis by regulating the ZBED6/STAT1/AIM2 axis through m1A demethylation. Clinical and translational medicine 0 41816893
2026 ALKBH3 m1A Demethylase Deficiency Reduces Alzheimer's Amyloid-β Pathology. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41816968

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