Affinage

FDXR

NADPH:adrenodoxin oxidoreductase, mitochondrial · UniProt P22570

Round 2 corrected
Length
491 aa
Mass
53.8 kDa
Annotated
2026-04-28
130 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FDXR is a mitochondrial FAD-containing NADPH:ferredoxin oxidoreductase that transfers electrons from NADPH to ferredoxins (FDX1/FDX2), supplying reducing equivalents for mitochondrial cytochrome P450-mediated steroidogenesis, heme biosynthesis, and iron–sulfur (Fe–S) cluster assembly (PMID:2845396, PMID:11053423, PMID:22101253). FDXR is transcriptionally induced by p53-family members (p53, p63, p73) upon DNA damage via a p53-response element in its promoter, sensitizing cells to ROS-dependent apoptosis, and reciprocally regulates p73 expression through an IRP2–IRE-mediated mRNA stability mechanism (PMID:12370809, PMID:32304229). Loss of FDXR causes mitochondrial iron overload, cytosolic iron depletion, impaired Fe–S enzyme activities, and mitochondrial membrane depolarization, which collectively underlie a progressive neurodegeneration (PMID:22101253, PMID:32499495). Biallelic loss-of-function FDXR mutations cause a human mitochondriopathy characterized by auditory neuropathy, optic atrophy, and neuroinflammation (PMID:28965846, PMID:30250212).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1988 High

    Molecular cloning established FDXR as a single-copy gene encoding a mitochondrial flavoprotein that initiates NADPH-dependent electron transfer to mitochondrial cytochromes P450, resolving the identity of the human adrenodoxin reductase.

    Evidence cDNA cloning, Southern blotting of somatic cell hybrids, and Northern blotting in human tissues

    PMID:2845396

    Open questions at the time
    • Catalytic mechanism and cofactor geometry not determined
    • Alternative splice-form functional significance unknown
    • Tissue-specific regulation uncharacterized
  2. 1991 High

    Mutagenesis of the electron-transfer partner ferredoxin identified specific acidic residues (Asp-76, Asp-79) required for FDXR binding, demonstrating that FDXR and P450scc share overlapping but distinct docking surfaces on ferredoxin, consistent with a shuttle model of sequential electron donation.

    Evidence Site-directed mutagenesis with reconstituted cholesterol side-chain cleavage assay

    PMID:1917982

    Open questions at the time
    • No structural visualization of the complex
    • Electron-transfer rate constants not measured
  3. 2000 High

    The crystal structure of the FDXR–adrenodoxin complex at 2.3 Å revealed the electrostatic protein–protein interface and placed the [2Fe–2S] cluster ~10 Å from the FAD isoalloxazine ring, defining the electron-transfer pathway at atomic resolution.

    Evidence X-ray crystallography of the bovine adrenodoxin reductase–adrenodoxin complex

    PMID:11053423

    Open questions at the time
    • Human FDXR structure not solved
    • Dynamics of domain rearrangement upon complex formation not resolved
    • Interaction with FDX2 (ISC pathway ferredoxin) not structurally characterized
  4. 2002 High

    Discovery that FDXR is a direct transcriptional target of p53, p63, and p73 connected the mitochondrial electron-transfer enzyme to the DNA damage response, revealing a feed-forward loop in which stress-activated p53-family members induce FDXR to amplify ROS-mediated apoptosis.

    Evidence Chromatin immunoprecipitation, luciferase reporters, and inducible FDXR overexpression with apoptosis assays in H1299 and HCT116 cells

    PMID:12370809

    Open questions at the time
    • Endogenous ROS source (electron leak site) not pinpointed
    • Whether p53-induced FDXR apoptosis requires ferredoxin partners not tested
  5. 2011 High

    Knockdown experiments established that FDXR is essential for Fe–S cluster biogenesis and cellular iron homeostasis, extending its function beyond steroidogenesis to a fundamental role in mitochondrial iron metabolism.

    Evidence siRNA knockdown in multiple human cell lines with aconitase/SDH activity assays and mitochondrial iron quantification

    PMID:22101253

    Open questions at the time
    • Whether FDXR acts exclusively through FDX2 for ISC pathway not distinguished from FDX1 contributions
    • Mechanism linking FDXR loss to mitochondrial iron import not identified
  6. 2017 High

    Identification of biallelic FDXR mutations in families with auditory neuropathy and optic atrophy established FDXR deficiency as a human Mendelian mitochondriopathy, confirmed by yeast complementation showing pathogenic variants fail to rescue the ARH1 deletion.

    Evidence Whole-exome sequencing across four families, yeast ARH1 complementation, fibroblast iron homeostasis assays

    PMID:28965846

    Open questions at the time
    • Genotype–phenotype correlation across different mutation types incomplete
    • Neuronal-specific vulnerability not mechanistically explained
  7. 2018 Medium

    A mouse model extended the human disease phenotype by demonstrating that FDXR deficiency drives neuroinflammation with gliosis in the CNS, suggesting that neurodegeneration involves an inflammatory component beyond simple metabolic failure.

    Evidence Fdxr mutant mouse brain histopathology and immunohistochemistry for gliosis and neurodegeneration markers

    PMID:30250212

    Open questions at the time
    • Causal versus secondary role of neuroinflammation not dissected
    • Specific inflammatory signaling pathways not identified
  8. 2020 High

    Mechanistic dissection revealed that FDXR, via FDX2, controls IRP2 levels which in turn destabilize TP73 mRNA through an IRE in the 3′-UTR, completing a bidirectional feedback loop between the p73 tumor suppressor and FDXR, and compound Fdxr/Trp73 heterozygous mice showed antagonistic genetic interaction on senescence and tumorigenesis.

    Evidence IRE mutagenesis, RNA stability assays, and compound Fdxr+/−;Trp73+/− mouse genetic epistasis

    PMID:32304229

    Open questions at the time
    • IRP2-IRE axis for p73 not validated in human cancer cohorts
    • Whether p53 is similarly regulated by this axis not tested
  9. 2020 High

    Fdxr-deficient mice exhibited mitochondrial membrane depolarization and optic axonal transport defects alongside mitochondrial iron overload, linking the iron-homeostasis defect mechanistically to mitochondrial dysfunction and neurodegeneration in vivo.

    Evidence Fdxr hypomorphic mouse model with mitochondrial membrane potential, iron quantification, and optic transport assays

    PMID:32499495

    Open questions at the time
    • Whether iron chelation rescues optic transport not tested
    • Relative contribution of Fe–S loss versus iron overload to membrane depolarization unknown
  10. 2023 Medium

    FDXR was found to promote mitochondrial fatty acid oxidation by supporting CPT1A expression in ER+ breast cancer, identifying a metabolic vulnerability wherein combined endocrine therapy and FAO inhibition synergistically suppressed tumor growth.

    Evidence siRNA knockdown, Seahorse FAO assay, and LC-MS metabolomics in ER+ breast cancer cell lines

    PMID:37207154

    Open questions at the time
    • Mechanism by which FDXR controls CPT1A expression not identified
    • Not replicated in independent cohorts or in vivo models
    • Whether this FAO role is cancer-specific or generalizable unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of human FDXR's differential engagement with FDX1 versus FDX2, the mechanism by which FDXR loss drives mitochondrial iron import and neuroinflammatory signaling, and whether therapeutic iron chelation or FAO modulation can rescue FDXR-deficient phenotypes.
  • Human FDXR crystal structure unavailable
  • FDX1 vs FDX2 selectivity determinants unresolved
  • Therapeutic interventions for FDXR-linked mitochondriopathy untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0140104 molecular carrier activity 3
Localization
GO:0005739 mitochondrion 5
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 2
Partners
CPT1AFDX1FDX2FHITIRP2TP53TP73

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 Human adrenodoxin reductase (FDXR) is encoded by a single gene on chromosome 17cen–q25 and produces two alternatively spliced mRNAs differing by 18 bases (6 codons) near the middle of the coding sequence. The protein is a mitochondrial flavoprotein that initiates electron transport from NADPH to mitochondrial cytochromes P450. cDNA cloning, Southern blotting of somatic cell hybrids, Northern blotting, RNase protection assay Proceedings of the National Academy of Sciences of the United States of America High 2845396
1990 The human FDXR gene spans ~12 kb and contains 12 exons; the first exon encodes the signal peptide and the second encodes the FAD-binding site, while exon 6 encodes the NADPH-binding site. Two mRNA forms arise by alternative splicing at the 5' end of exon 7, adjacent to the NADPH-binding site. The promoter lacks TATA/CAAT boxes but contains six GGGCGGG (Sp1) motifs, consistent with a housekeeping gene. Genomic cloning, restriction mapping, DNA sequencing, RNase protection assay Proceedings of the National Academy of Sciences of the United States of America High 2236061
1991 The FDXR gene (adrenodoxin reductase) was mapped to chromosome 17q24–q25 by in situ hybridization, and the ferredoxin (adrenodoxin) gene was mapped to 11q22, establishing that none of the steroidogenic enzyme genes are closely linked to one another. In situ hybridization on human chromosomes DNA and cell biology High 1863359
1991 Site-directed mutagenesis of human ferredoxin (FDX, the direct electron-transfer partner of FDXR) identified Asp-76 and Asp-79 as residues critical for binding to both FDXR (ferredoxin reductase) and cytochrome P450scc, while other acidic residues (Asp-72, Glu-73) caused differential effects on FDXR vs. P450scc binding, indicating that the two binding interfaces overlap but are not identical. This supports a shuttle model in which ferredoxin alternately docks with FDXR and P450scc. Site-directed mutagenesis, in vitro binding assays, cholesterol side-chain cleavage reconstitution assay The Journal of biological chemistry High 1917982
2000 Crystal structure of the adrenodoxin reductase (AR/FDXR ortholog)–adrenodoxin complex at 2.3 Å resolution revealed the protein–protein interaction interface: key contacts involve Asp-79, Asp-76, Asp-72, and Asp-39 of adrenodoxin with Arg-211, Arg-240, Arg-244, and Lys-27 of the reductase. The [2Fe-2S] cluster of adrenodoxin and the isoalloxazine ring of FAD in the reductase are ~10 Å apart, defining the likely electron-transfer route. Complex formation induces a slight domain rearrangement in the reductase. X-ray crystallography (2.3 Å resolution crystal structure of the complex) The Journal of biological chemistry High 11053423
2002 FDXR (ferredoxin reductase) was identified as a transcriptional target of the p53 family (p53, p63, p73). FDXR is induced by DNA damage in a p53-dependent manner; a p53 response element in the FDXR promoter is directly bound by p53, p63α/γ, and p73α/β in vivo. p53 binding increases histone H3 and H4 acetylation at the FDXR promoter. Overexpression of FDXR sensitizes lung (H1299) and colorectal (HCT116) carcinoma cells to apoptosis induced by 5-fluorouracil, doxorubicin, and H₂O₂, suggesting a feed-forward loop in which cellular stress activates p53→FDXR→ROS-mediated apoptosis. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, tetracycline-inducible overexpression, cell viability/apoptosis assays Oncogene High 12370809
2003 FDXR (adrenodoxin reductase) protein and mRNA are expressed in human epidermis, hair follicles, sebaceous ducts, and sebaceous glands, demonstrating that human skin is a steroidogenic tissue that expresses the complete P450scc electron-transport system (FDXR–adrenodoxin–P450scc). Immunohistochemistry, Western blotting, quantitative RT-PCR, gene array The Journal of investigative dermatology Medium 12787114
2011 siRNA knockdown of FDXR (the sole human ferredoxin reductase) in multiple human cell lines disrupted iron-sulfur (Fe-S) cluster assembly, caused mitochondrial iron overload, and produced cytosolic iron depletion, demonstrating that FDXR is required for maintaining normal mitochondrial and cellular iron homeostasis as well as Fe-S cluster biogenesis. siRNA knockdown, activity assays for Fe-S cluster enzymes (aconitase, succinate dehydrogenase), mitochondrial iron quantification, Western blotting Biochimica et biophysica acta High 22101253
2017 Biallelic loss-of-function mutations in FDXR cause auditory neuropathy and optic atrophy in humans. Mutant FDXR fibroblasts show deregulated iron homeostasis and indirect evidence of mitochondrial iron overload. Functional complementation of the yeast ARH1 (FDXR ortholog) deletion strain by human wild-type FDXR cDNA (but not pathogenic mutants) confirmed pathogenicity. FDXR is identified as the sole human ferredoxin reductase involved in iron-sulfur cluster (ISC) biosynthesis and heme formation. Whole-exome sequencing, fibroblast iron homeostasis assays, yeast complementation of ARH1 deletion strain American journal of human genetics High 28965846
2017 The co-chaperone HSC20 directly binds LYRM7 (an assembly factor for the Rieske Fe-S protein UQCRFS1 of Complex III), and the HSC20–HSPA9–holo-ISCU scaffold complex interacts with the pre-assembled UQCRFS1–LYRM7 intermediate to deliver the Fe-S cluster. This pathway is downstream of the FDXR–FDX electron-transfer system that reduces the ISCU scaffold. Five Fe-S cluster subunits of Complex I also acquire clusters through HSC20, demonstrating a central role for this cochaperone-scaffold in respiratory chain assembly. Co-immunoprecipitation, affinity purification–mass spectrometry, siRNA knockdown, enzymatic activity assays Cell metabolism High 28380382
2018 Biallelic FDXR mutations cause mitochondriopathy with peripheral neuropathy and optic atrophy associated with neuroinflammation. Fdxr mutant mouse brain tissues show increased astrocytes (gliosis) and elevated markers of neurodegeneration, indicating that FDXR deficiency causes central nervous system pathology through an inflammatory mechanism. Patient clinical evaluation, mouse model histopathology, immunohistochemistry for neurodegeneration and gliosis markers, brain autopsy Journal of human genetics Medium 30250212
2019 Fhit protein (tumor suppressor) forms a complex with FDXR in the mitochondria, identified by protein cross-linking followed by proteomics. The Fhit–FDXR interaction occurs at electron transport chain complex III, where FDXR transfers electrons from NADPH to cytochrome P450 via ferredoxin. Overexpression of Fhit in Fhit-deficient cancer cells modulates intracellular reactive oxygen species (ROS), increasing ROS and apoptosis under oxidative stress; Fhit-negative cells escape ROS-induced apoptosis. HSP60/10 chaperonin pair is implicated in Fhit mitochondrial import. Protein cross-linking, proteomics (mass spectrometry), co-immunoprecipitation, ROS measurement, apoptosis assays, in vitro and in vivo cancer cell models Cell death & disease Medium 30770797
2020 Loss of FDXR, via its electron-carrier FDX2, increases expression of iron-regulatory protein 2 (IRP2), which subsequently destabilizes TP73 mRNA by binding to an iron response element (IRE) in the TP73 3'UTR, thereby repressing p73 protein expression. Conversely, FDXR is transcriptionally regulated by p73, creating a feedback axis. Compound Trp73+/−;Fdxr+/− mice showed increased cellular senescence but fewer tumors than single heterozygotes, suggesting antagonistic genetic interaction. Genetically modified mouse models, MEF senescence assays, qRT-PCR, Western blotting, IRE deletion/mutation constructs, RNA stability assays The Journal of pathology High 32304229
2020 FDXR mutation causes significant optic transport defects, mitochondrial iron overload, and depolarization of the mitochondrial membrane in a mouse model, further supporting the hypothesis that FDXR's critical role in iron homeostasis underlies neurodegeneration and optic atrophy. Neurodegenerative cell loss in the CNS was also demonstrated. Fdxr hypomorphic mouse model, optic transport assays, mitochondrial membrane potential measurements, mitochondrial iron quantification, histological analysis Cell death & disease High 32499495
2020 At least 14 FDXR transcript variants are expressed in human blood, all upregulated after ionizing radiation (IR) in a dose-dependent manner. FDXR-201 and FDXR-208 are the most highly IR-responsive; FDXR-218 and FDXR-219 have no detectable basal expression but are induced by IR. In vitro inflammation transiently counteracted the IR transcriptional response early after exposure. Upregulation was confirmed in vivo in radiotherapy patients. Quantitative RT-PCR with variant-specific primers, nanopore full-length sequencing, in vivo radiotherapy patient blood samples International journal of molecular sciences Medium 33113898
2023 FDXR promotes mitochondrial fatty acid oxidation (FAO) by supporting CPT1A expression in ER+ breast cancer cells. Depletion of FDXR suppressed CPT1A expression and reduced FAO-mediated oxygen consumption. Endocrine treatment increased both FDXR and CPT1A levels. The FDXR–CPT1A–FAO axis was required for growth of both primary and endocrine-resistant breast cancer cells, and combining endocrine therapy with the FAO inhibitor etomoxir synergistically inhibited cell growth. LC-MS/MS metabolite profiling, RNA microarray, Seahorse XF24 FAO assay, siRNA knockdown, MTS/colony formation assays, 2D and anchorage-independent growth assays Frontiers in oncology Medium 37207154

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2002 Androgen receptor (AR) coregulators: an overview. Endocrine reviews 706 11943742
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2015 Plasma AR and abiraterone-resistant prostate cancer. Science translational medicine 385 26537258
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2008 AR, the cell cycle, and prostate cancer. Nuclear receptor signaling 270 18301781
2021 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. Cell metabolism 239 34800366
2003 Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1). The Journal of investigative dermatology 224 12787114
2013 Androgen receptor (AR) differential roles in hormone-related tumors including prostate, bladder, kidney, lung, breast and liver. Oncogene 180 23873027
2002 The ferredoxin reductase gene is regulated by the p53 family and sensitizes cells to oxidative stress-induced apoptosis. Oncogene 178 12370809
2008 Diverse roles of androgen receptor (AR) domains in AR-mediated signaling. Nuclear receptor signaling 176 18612376
2019 Discovery of Highly Potent and Efficient PROTAC Degraders of Androgen Receptor (AR) by Employing Weak Binding Affinity VHL E3 Ligase Ligands. Journal of medicinal chemistry 162 31804827
2011 Both human ferredoxins 1 and 2 and ferredoxin reductase are important for iron-sulfur cluster biogenesis. Biochimica et biophysica acta 160 22101253
1991 Site-specific mutations in human ferredoxin that affect binding to ferredoxin reductase and cytochrome P450scc. The Journal of biological chemistry 146 1917982
2000 Adrenodoxin reductase-adrenodoxin complex structure suggests electron transfer path in steroid biosynthesis. The Journal of biological chemistry 143 11053423
2017 AR Signaling and the PI3K Pathway in Prostate Cancer. Cancers 140 28420128
2012 Androgen receptor (AR) aberrations in castration-resistant prostate cancer. Molecular and cellular endocrinology 135 22245783
2019 TBCRC 032 IB/II Multicenter Study: Molecular Insights to AR Antagonist and PI3K Inhibitor Efficacy in Patients with AR+ Metastatic Triple-Negative Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 128 31822498
1991 Regional mapping of genes encoding human steroidogenic enzymes: P450scc to 15q23-q24, adrenodoxin to 11q22; adrenodoxin reductase to 17q24-q25; and P450c17 to 10q24-q25. DNA and cell biology 122 1863359
2016 Cooperative Dynamics of AR and ER Activity in Breast Cancer. Molecular cancer research : MCR 116 27565181
2020 International expert consensus on the management of allergic rhinitis (AR) aggravated by air pollutants: Impact of air pollution on patients with AR: Current knowledge and future strategies. The World Allergy Organization journal 114 32256939
2018 Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses. Nature communications 114 30190514
2010 CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation. Molecular endocrinology (Baltimore, Md.) 114 20980437
2002 AR and ER interaction with a p21-activated kinase (PAK6). Molecular endocrinology (Baltimore, Md.) 114 11773441
2002 Inhibition of androgen receptor (AR) function by the reproductive orphan nuclear receptor DAX-1. Molecular endocrinology (Baltimore, Md.) 113 11875111
2019 Everything You Always Wanted to Know about β3-AR * (* But Were Afraid to Ask). Cells 112 30995798
2020 Binding pathway determines norepinephrine selectivity for the human β1AR over β2AR. Cell research 107 33093660
2021 Androgen receptor (AR) heterogeneity in prostate cancer and therapy resistance. Cancer letters 104 34118355
2011 Reversal of doxorubicin-resistance by multifunctional nanoparticles in MCF-7/ADR cells. Journal of controlled release : official journal of the Controlled Release Society 103 21435362
2023 Landscape of prostate-specific membrane antigen heterogeneity and regulation in AR-positive and AR-negative metastatic prostate cancer. Nature cancer 96 37038004
2016 Role of SUMO activating enzyme in cancer stem cell maintenance and self-renewal. Nature communications 95 27465491
2017 AR Signaling in Breast Cancer. Cancers 93 28245550
1988 Human adrenodoxin reductase: two mRNAs encoded by a single gene on chromosome 17cen----q25 are expressed in steroidogenic tissues. Proceedings of the National Academy of Sciences of the United States of America 90 2845396
2021 A noncanonical AR addiction drives enzalutamide resistance in prostate cancer. Nature communications 82 33750801
2017 A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I-III. Cell metabolism 78 28380382
2020 KIF15-Mediated Stabilization of AR and AR-V7 Contributes to Enzalutamide Resistance in Prostate Cancer. Cancer research 76 33277366
2015 β2-AR signaling controls trastuzumab resistance-dependent pathway. Oncogene 76 25798840
2019 The midbody interactome reveals unexpected roles for PP1 phosphatases in cytokinesis. Nature communications 74 31586073
2017 FDXR Mutations Cause Sensorial Neuropathies and Expand the Spectrum of Mitochondrial Fe-S-Synthesis Diseases. American journal of human genetics 67 28965846
2021 Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy. Acta pharmaceutica Sinica. B 66 35256949
2020 Analysis of β2AR-Gs and β2AR-Gi complex formation by NMR spectroscopy. Proceedings of the National Academy of Sciences of the United States of America 66 32868434
2022 Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery. Nature communications 65 35831314
2017 A Role for Mitochondrial Translation in Promotion of Viability in K-Ras Mutant Cells. Cell reports 64 28700943
2015 ERG/AKR1C3/AR Constitutes a Feed-Forward Loop for AR Signaling in Prostate Cancer Cells. Clinical cancer research : an official journal of the American Association for Cancer Research 64 25754347
2022 MYC multimers shield stalled replication forks from RNA polymerase. Nature 63 36424410
2016 Androgen receptor (AR) in cardiovascular diseases. The Journal of endocrinology 62 26769913
1990 Cloning and sequence of the human adrenodoxin reductase gene. Proceedings of the National Academy of Sciences of the United States of America 56 2236061
1988 Molecular cloning and sequence analysis of human placental ferredoxin. Archives of biochemistry and biophysics 53 2969697
2016 Targeting Androgen Receptor (AR)→IL12A Signal Enhances Efficacy of Sorafenib plus NK Cells Immunotherapy to Better Suppress HCC Progression. Molecular cancer therapeutics 52 26939703
2016 Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer. Hormones & cancer 50 26728473
2016 Identification of an AR Mutation-Negative Class of Androgen Insensitivity by Determining Endogenous AR Activity. The Journal of clinical endocrinology and metabolism 50 27583472
2016 The HIF/PHF8/AR axis promotes prostate cancer progression. Oncogenesis 50 27991916
2022 Positive epigenetic regulation loop between AR and NSUN2 promotes prostate cancer progression. Clinical and translational medicine 48 36169095
2021 AR Splicing Variants and Resistance to AR Targeting Agents. Cancers 48 34071114
2018 Molecules targeting the androgen receptor (AR) signaling axis beyond the AR-Ligand binding domain. Medicinal research reviews 47 30565725
2016 A Whole Blood Assay for AR-V7 and ARv567es in Patients with Prostate Cancer. The Journal of urology 47 27449259
2019 Fhit-Fdxr interaction in the mitochondria: modulation of reactive oxygen species generation and apoptosis in cancer cells. Cell death & disease 46 30770797
2018 The deubiquitylating enzyme UCHL3 regulates Ku80 retention at sites of DNA damage. Scientific reports 46 30559450
2012 Methylation of AR locus does not always reflect X chromosome inactivation state. Blood 44 22286197
2002 Domain interactions between coregulator ARA(70) and the androgen receptor (AR). Molecular endocrinology (Baltimore, Md.) 43 11818501
2014 The transcriptional programme of the androgen receptor (AR) in prostate cancer. BJU international 42 24053777
2021 LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance. Cell death & disease 41 34545063
2001 The androgen receptor (AR) in syndromes of androgen insensitivity and in prostate cancer. The Journal of steroid biochemistry and molecular biology 41 11384871
2008 Role of CYP epoxygenases in A2A AR-mediated relaxation using A2A AR-null and wild-type mice. American journal of physiology. Heart and circulatory physiology 40 18805895
2022 METTL3 boosts glycolysis and cardiac fibroblast proliferation by increasing AR methylation. International journal of biological macromolecules 39 36370857
2006 Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells. Cancer research 39 17178871
2019 [EGFR-TKI ADR Management Chinese Expert Consensus]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 38 30827323
2022 Regulation of AR mRNA translation in response to acute AR pathway inhibition. Nucleic acids research 37 34939643
2015 Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status. Oncotarget 37 26304926
2016 Cell cycle-coupled expansion of AR activity promotes cancer progression. Oncogene 36 27669432
2015 Infiltrating neutrophils promote renal cell carcinoma (RCC) proliferation via modulating androgen receptor (AR) → c-Myc signals. Cancer letters 36 26231735
2017 Multimodal actions of the phytochemical sulforaphane suppress both AR and AR-V7 in 22Rv1 cells: Advocating a potent pharmaceutical combination against castration-resistant prostate cancer. Oncology reports 35 28901514
2004 Induction of apoptosis by ar-turmerone on various cell lines. International journal of molecular medicine 35 15254774
2014 TBLR1 as an androgen receptor (AR) coactivator selectively activates AR target genes to inhibit prostate cancer growth. Endocrine-related cancer 34 24243687
2020 FDXR regulates TP73 tumor suppressor via IRP2 to modulate aging and tumor suppression. The Journal of pathology 33 32304229
2020 Integrated analysis of the molecular pathogenesis of FDXR-associated disease. Cell death & disease 32 32499495
2018 Biallelic mutations in FDXR cause neurodegeneration associated with inflammation. Journal of human genetics 32 30250212
2024 ALDH1A1 drives prostate cancer metastases and radioresistance by interplay with AR- and RAR-dependent transcription. Theranostics 31 38169509
2021 G3BP1 inhibits Cul3SPOP to amplify AR signaling and promote prostate cancer. Nature communications 31 34795264
2020 ACK1-AR and AR-HOXB13 signaling axes: epigenetic regulation of lethal prostate cancers. NAR cancer 31 32885168
2018 Membrane-associated androgen receptor (AR) potentiates its transcriptional activities by activating heat shock protein 27 (HSP27). The Journal of biological chemistry 31 29934310
2015 Rutaecarpine and evodiamine selected as β1-AR inhibitor candidates using β1-AR/CMC-offline-UPLC/MS prevent cardiac ischemia-reperfusion injury via energy modulation. Journal of pharmaceutical and biomedical analysis 31 26263059
2013 Cholesterol-β1 AR interaction versus cholesterol-β2 AR interaction. Proteins 29 24265091
2020 In Vivo Validation of Alternative FDXR Transcripts in Human Blood in Response to Ionizing Radiation. International journal of molecular sciences 28 33113898
2017 Aurora Kinase A Promotes AR Degradation via the E3 Ligase CHIP. Molecular cancer research : MCR 28 28536143
2016 Salubrinal-Mediated Upregulation of eIF2α Phosphorylation Increases Doxorubicin Sensitivity in MCF-7/ADR Cells. Molecules and cells 28 26743901
2017 Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells. Cancer immunology research 27 29051161
2014 Association study of ERβ, AR, and CYP19A1 genes and MtF transsexualism. The journal of sexual medicine 27 25124466
2021 Chemical Degradation of Androgen Receptor (AR) Using Bicalutamide Analog-Thalidomide PROTACs. Molecules (Basel, Switzerland) 26 33926033
2020 Sex, androgens and regulation of pulmonary AR, TMPRSS2 and ACE2. bioRxiv : the preprint server for biology 26 33083800
2021 Targeting KDM4A-AS1 represses AR/AR-Vs deubiquitination and enhances enzalutamide response in CRPC. Oncogene 24 34759344
2014 MEIS1 functions as a potential AR negative regulator. Experimental cell research 24 25158280
2021 Undesirable Status of Prostate Cancer Cells after Intensive Inhibition of AR Signaling: Post-AR Era of CRPC Treatment. Biomedicines 23 33921329
2020 Natural Compounds as Source of Aldose Reductase (AR) Inhibitors for the Treatment of Diabetic Complications: A Mini Review. Current drug metabolism 23 33069193
2019 Preclinical study using androgen receptor (AR) degradation enhancer to increase radiotherapy efficacy via targeting radiation-increased AR to better suppress prostate cancer progression. EBioMedicine 23 30692044
2019 Revisiting the relationships of 2D:4D with androgen receptor (AR) gene and current testosterone levels: Replication study and meta-analyses. Journal of neuroscience research 23 31359506
2019 Comparative Analysis of AR Variant AR-V567es mRNA Detection Systems Reveals Eminent Variability and Questions the Role as a Clinical Biomarker in Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 21 30992298
2006 Hic-5/ARA55: a prostate stroma-specific AR coactivator. Steroids 21 17166536
2022 OTUD6A promotes prostate tumorigenesis via deubiquitinating Brg1 and AR. Communications biology 20 35233061
2021 Huaier Extract Inhibits Prostate Cancer Growth via Targeting AR/AR-V7 Pathway. Frontiers in oncology 20 33708629
2018 Targeting P-Glycoprotein: Nelfinavir Reverses Adriamycin Resistance in K562/ADR Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 20 30497065
2014 SUMO-specific protease 1 modulates cadmium-augmented transcriptional activity of androgen receptor (AR) by reversing AR SUMOylation. Toxicology letters 20 25014244
2018 AR Signaling in Human Malignancies: Prostate Cancer and Beyond. Cancers 19 29346310
2013 Direct interaction between AR and PAK6 in androgen-stimulated PAK6 activation. PloS one 19 24130878
1998 Variants in the alpha2A AR adrenergic receptor gene in psychiatric patients. American journal of medical genetics 19 9754626
2019 Non-nuclear AR Signaling in Prostate Cancer. Frontiers in chemistry 18 31616657
2019 DUSP22 suppresses prostate cancer proliferation by targeting the EGFR-AR axis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 31693867
2018 CNPY2 inhibits MYLIP-mediated AR protein degradation in prostate cancer cells. Oncotarget 18 29707137
2019 ASC-J9® increases the bladder cancer chemotherapy efficacy via altering the androgen receptor (AR) and NF-κB survival signals. Journal of experimental & clinical cancer research : CR 17 31234917
2017 Improved androgen specificity of AR-EcoScreen by CRISPR based glucocorticoid receptor knockout. Toxicology in vitro : an international journal published in association with BIBRA 17 28803809
2017 Androgen receptor (AR) cistrome in prostate differentiation and cancer progression. American journal of clinical and experimental urology 17 29181434
2016 Lgr4 promotes prostate tumorigenesis through the Jmjd2a/AR signaling pathway. Experimental cell research 17 27743893
2022 Increased AR expression in castration-resistant prostate cancer rapidly induces AR signaling reprogramming with the collaboration of EZH2. Frontiers in oncology 16 36408179
2021 Androgen receptor (AR) decreases HCC cells migration and invasion via miR-325/ACP5 signaling. Journal of Cancer 16 33753989
2020 Coordinated AR and microRNA regulation in prostate cancer. Asian journal of urology 16 32742925
2024 Capsaicin induces ATP-dependent thermogenesis via the activation of TRPV1/β3-AR/α1-AR in 3T3-L1 adipocytes and mouse model. Archives of biochemistry and biophysics 15 38531438
2023 FDXR drives primary and endocrine-resistant tumor cell growth in ER+ breast cancer via CPT1A-mediated fatty acid oxidation. Frontiers in oncology 15 37207154
2018 Paris saponin VII reverses chemoresistance in breast MCF-7/ADR cells. Journal of ethnopharmacology 15 30552993
2021 Androgen receptor (AR) antagonism triggers acute succinate-mediated adaptive responses to reactivate AR signaling. EMBO molecular medicine 13 33709547
2019 Ligand induced dissociation of the AR homodimer precedes AR monomer translocation to the nucleus. Scientific reports 13 31723170
2017 ELF5-Mediated AR Activation Regulates Prostate Cancer Progression. Scientific reports 13 28287091