Affinage

CYP24A1

1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial · UniProt Q07973

Length
514 aa
Mass
58.9 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CYP24A1 is a mitochondrial cytochrome P450 enzyme that serves as the principal catabolic regulator of vitamin D homeostasis by catalyzing sequential multi-step oxidation of both 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 through C-24 and C-23 hydroxylation pathways, using adrenodoxin and adrenodoxin reductase as electron transfer partners; human CYP24A1 utilizes both pathways while rat CYP24A1 preferentially employs C-24 oxidation, a species difference governed by residues T416 and I500 (PMID:11012668, PMID:16617161, PMID:24893882). Transcriptional regulation is driven by 1,25(OH)2D3 acting through VDR-RXR heterodimers at two synergistic proximal VDREs and kidney-specific downstream enhancers, with cooperative input from ERK1/2- and ERK5-mediated phosphorylation of RXRα and Ets-1, PTH signaling via cAMP, FGF23, PXR activation by xenobiotics, calcitonin via PKA/PKCζ/Ras, and chromatin remodeling involving PRMT1/CARM1-mediated histone methylation (PMID:8939905, PMID:12048211, PMID:31629064, PMID:39363152, PMID:15630458, PMID:14765994, PMID:31868234). CYP24A1 expression is subject to epigenetic silencing through promoter CpG methylation and repressive histone marks (H3K9me2), which in tumor cells blocks VDR recruitment and abrogates vitamin D-mediated feedback (PMID:17244627, PMID:20587525). Loss-of-function mutations in CYP24A1 abolish 24-hydroxylase activity and cause idiopathic infantile hypercalcemia characterized by inability to degrade 1,25(OH)2D3 (PMID:21675912).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Identification of two proximal VDREs acting synergistically in the CYP24 promoter established that 1,25(OH)2D3 induces its own catabolism through a direct VDR-RXR transcriptional feedback loop, resolving how vitamin D autoregulates its degradation.

    Evidence Promoter-reporter mutagenesis in multiple cell lines with EMSA for VDR-RXR binding

    PMID:8939905

    Open questions at the time
    • Upstream enhancer elements not yet mapped
    • Chromatin context of VDRE activity not addressed
  2. 1998 High

    Demonstration that PTH synergistically enhances CYP24 transcription via cAMP signaling revealed that calcium-regulating hormones converge on CYP24 to fine-tune vitamin D catabolism in bone cells.

    Evidence Nuclear run-on, promoter-reporter, and cAMP mimicry in UMR106 osteoblastic cells

    PMID:9681485

    Open questions at the time
    • Cis-elements mediating PTH/cAMP response not identified
    • Kidney-specific PTH effects not tested
  3. 2000 High

    Reconstitution of human CYP24A1 showed it catalyzes both C-23 and C-24 multi-step oxidation pathways for vitamin D metabolites while rat CYP24A1 lacks C-23 activity, defining the enzyme's complete catalytic repertoire and a major species difference.

    Evidence In vitro reconstitution with adrenodoxin/adrenodoxin reductase in E. coli; HPLC/MS metabolite profiling

    PMID:11012668

    Open questions at the time
    • Structural basis for species difference unknown
    • Membrane context not reconstituted
  4. 2002 High

    Discovery that ERK1/2 phosphorylates RXRα at S260 and ERK5 phosphorylates Ets-1 at T38, both required for full CYP24 transactivation, established that MAPK signaling integrates with VDR-dependent transcription to modulate vitamin D catabolism.

    Evidence Dominant-negative kinases, pharmacological inhibitors, in vitro phosphorylation, site-directed mutagenesis, and promoter-reporter assays

    PMID:12048211

    Open questions at the time
    • Upstream signals activating ERK5 for CYP24 induction not identified
    • In vivo relevance not tested
  5. 2004 High

    Mutagenesis of F249, T416, and I500 identified key active-site residues controlling substrate orientation and the species-specific balance between C-23 and C-24 oxidation pathways, while CYP24 knockout mice confirmed that CYP24 is the sole source of 24,25(OH)2D3 in vivo.

    Evidence Site-directed mutagenesis with kinetic analysis in E. coli; CYP24 KO mouse metabolite profiling by LC/MS

    PMID:15111121 PMID:15225763 PMID:16617161

    Open questions at the time
    • Crystal structure not available to confirm substrate docking models
    • Contribution of membrane environment to substrate access not addressed
  6. 2004 High

    Calcitonin was shown to induce CYP24 via PKA, atypical PKCζ, and Ras through Sp1/NF-Y promoter elements, identifying a third hormonal input distinct from VDR-mediated and PTH-mediated regulation.

    Evidence Pharmacological inhibitors, dominant-negative kinases, and promoter-reporter assays in HEK-293 cells

    PMID:14765994

    Open questions at the time
    • In vivo renal significance of calcitonin-mediated CYP24 induction not confirmed
    • Direct calcitonin receptor signaling to Sp1/NF-Y not fully resolved
  7. 2005 High

    PXR was identified as a novel transcriptional activator of CYP24 through the same proximal VDREs, providing a mechanism by which xenobiotics (rifampicin, hyperforin) can accelerate vitamin D catabolism and potentially cause drug-induced vitamin D deficiency.

    Evidence Promoter-reporter with PXR, 24-hydroxylase activity in human hepatocytes, in vivo mouse metabolite measurement

    PMID:15630458

    Open questions at the time
    • Relative contribution of PXR vs VDR at CYP24 VDREs under physiological conditions unclear
    • Clinical significance not quantified
  8. 2005 High

    ChIP mapping across the CYP24 locus revealed VDR binding to four distinct regions including three novel upstream sites, with temporally ordered recruitment of RXR, coactivators, Mediator, and RNA Pol II, establishing that CYP24 induction requires coordinated multi-region chromatin remodeling.

    Evidence Comprehensive ChIP and re-ChIP across 25 contiguous genomic regions with reporter validation

    PMID:15919092

    Open questions at the time
    • Functional necessity of individual upstream VDR-binding regions not tested by deletion
    • 3D chromatin architecture not addressed
  9. 2007 High

    CpG methylation of the CYP24 promoter was shown to silence expression in tumor-derived endothelial cells by preventing VDR recruitment, revealing an epigenetic mechanism that uncouples vitamin D catabolism from VDR signaling in certain cancer contexts.

    Evidence Bisulfite sequencing, methylation-specific PCR, ChIP for VDR, 5-aza-dC treatment, siRNA rescue

    PMID:17244627

    Open questions at the time
    • Generality of CYP24A1 methylation across cancer types not systematically assessed
    • Mechanism of de novo methylation not identified
  10. 2010 High

    Repressive histone marks (H3K9me2) were shown to cooperate with DNA methylation in silencing CYP24A1 in prostate cancer, and HDAC/DNMT inhibitors could reactivate expression, extending the epigenetic regulatory model beyond DNA methylation alone.

    Evidence Bisulfite pyrosequencing, ChIP-qPCR for histone marks and VDR, DNMT and HDAC inhibitor treatments

    PMID:20587525

    Open questions at the time
    • Writers of H3K9me2 at CYP24A1 not identified
    • Therapeutic window for epigenetic reactivation not explored
  11. 2011 High

    Identification of loss-of-function CYP24A1 mutations in families with idiopathic infantile hypercalcemia proved that CYP24A1 is non-redundant for vitamin D catabolism in humans and that its absence causes pathological hypercalcemia.

    Evidence Candidate-gene sequencing in affected families; functional characterization of mutations in mammalian expression system

    PMID:21675912

    Open questions at the time
    • Genotype-phenotype correlations across mutation spectrum incomplete
    • Contribution of heterozygous carrier status to milder phenotypes not resolved
  12. 2014 High

    Kinetic reconstitution in phospholipid vesicles demonstrated that CYP24A1 catalytic rate depends on substrate concentration in the membrane phase, and pathway intermediates compete for the active site causing their accumulation, explaining why multiple metabolites are detected in vivo.

    Evidence In vitro reconstitution in phospholipid vesicles with Km/kcat determination for each C24-oxidation intermediate

    PMID:24893882

    Open questions at the time
    • Role of inner mitochondrial membrane lipid composition not tested
    • Product release mechanism not characterized
  13. 2014 Medium

    An IRES element in the CYP24A1 5′UTR was shown to enable translational upregulation under inflammatory conditions via PI3K/Akt signaling, revealing a post-transcriptional layer of CYP24A1 regulation beyond the well-characterized transcriptional mechanisms.

    Evidence Polysome profiling, bicistronic IRES reporter, PI3K inhibition, constitutively active Akt

    PMID:24416388

    Open questions at the time
    • IRES trans-acting factors not identified
    • In vivo relevance during inflammation not confirmed
    • Independent replication in another system not reported
  14. 2019 High

    In vivo deletion of kidney-specific downstream enhancers (DS1) and proximal VDREs in mice resolved how PTH, FGF23, and 1,25(OH)2D3 use distinct cis-regulatory modules: PTH suppresses CYP24A1 through DS1 independently of proximal VDREs, while FGF23 acts through both, and intestinal induction requires the proximal VDREs.

    Evidence CRISPR-based enhancer and VDRE deletion mouse models with hormone treatments and tissue-specific gene expression analysis

    PMID:31629064 PMID:39363152

    Open questions at the time
    • Trans-acting factors mediating FGF23 response at DS1 not identified
    • Chromatin looping between DS1 and proximal promoter not demonstrated
  15. 2019 Medium

    Chromatin remodeling at the CYP24A1 promoter was shown to involve a switch from PRMT5-deposited repressive H4R3me2s to PRMT1/CARM1-deposited activating arginine methylation marks upon 1,25(OH)2D3 stimulation, adding arginine methyltransferases to the coactivator cascade.

    Evidence ChIP-qPCR for multiple histone arginine and lysine marks, siRNA knockdown of PRMTs in osteoblastic cells

    PMID:31868234

    Open questions at the time
    • Order of PRMT recruitment relative to HATs and Mediator not resolved
    • Independent replication in non-osteoblastic cell types lacking
  16. 2021 High

    CRISPR-generated Cyp24a1 KO rats confirmed CYP24A1 as the sole enzyme producing 23,25(OH)2D3, and showed that downstream conversion to 25(OH)D3-26,23-lactone requires CYP3A rather than CYP24A1, clarifying the division of labor in the C-23 pathway.

    Evidence Cyp24a1 KO rats with oral vitamin D metabolite administration; recombinant CYP assays; ketoconazole inhibition; LC/MS

    PMID:33865853

    Open questions at the time
    • Physiological significance of the C-23 pathway relative to C-24 in humans not quantified in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution crystal structure of human CYP24A1 with substrate bound is still lacking, and the structural basis for the dual C-23/C-24 pathway selectivity, the mechanism of sequential multi-step oxidation without substrate release, and the integration of transcriptional, translational, and epigenetic regulation in specific tissues remain incompletely understood.
  • No crystal structure with substrate to validate mutagenesis-based models
  • Relative quantitative contributions of C-23 vs C-24 pathways in human tissues not measured in vivo
  • How tissue-specific enhancer usage is established during development is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 6 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005739 mitochondrion 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1430728 Metabolism 4 R-HSA-4839726 Chromatin organization 4 R-HSA-162582 Signal Transduction 3
Partners
CARM1ETS1LSHPRMT1PXRRXRVDR

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Human CYP24A1 expressed in E. coli catalyzes both C-23 and C-24 hydroxylation pathways for 25(OH)D3 and 1α,25(OH)2D3, converting them through multiple sequential oxidation steps; rat CYP24A1 shows almost no C-23 hydroxylation pathway, demonstrating species-based mechanistic difference. In vitro reconstitution with adrenodoxin/adrenodoxin reductase in E. coli expression system; HPLC and mass spectrometric analysis of metabolites European journal of biochemistry High 11012668
2004 Rat CYP24A1 F249 in the F-helix is required for proper substrate binding and alignment in the active site for C-23 and C-24 oxidation reactions; F249T, F249A, and F249Y mutants showed reduced substrate-binding affinity and specific catalytic defects. The 1α- and 25-hydroxyl groups are the major determinants for high-affinity binding. Site-directed mutagenesis of recombinant rat CYP24A1 expressed in E. coli; substrate-induced spectral shift assays; kinetic analysis Archives of biochemistry and biophysics High 15111121
2006 Amino acid residues T416 and I500 in rat CYP24A1 are responsible for the species-based difference in C-23 oxidation pathway activity; mutants T416M and I500T (rat→human) conferred C-23 oxidation capacity, suggesting these residues govern substrate orientation in the active site. Site-directed mutagenesis of rat CYP24A1 expressed in E. coli; metabolite analysis; 3D homology modeling Molecular pharmacology High 16617161
2014 Human CYP24A1 expressed in E. coli and reconstituted in phospholipid vesicles metabolizes 1,25(OH)2D3 through the C24-oxidation pathway via sequential steps; substrate concentration in the membrane phase (not aqueous) determines rate of metabolism, and intermediates compete with substrate for the active site causing accumulation. In vitro reconstitution in phospholipid vesicles; kinetic analysis (Km, kcat) for each C24-oxidation pathway intermediate; enzymatic production of pathway intermediates using rat CYP24A1 The FEBS journal High 24893882
2011 Loss-of-function mutations in CYP24A1 cause complete absence of 25-hydroxyvitamin D3 24-hydroxylase activity, resulting in inability to degrade 1,25(OH)2D3 and causing idiopathic infantile hypercalcemia; functional characterization in mammalian expression system confirmed complete loss of enzymatic function for all identified mutations. Candidate-gene sequencing; functional characterization in mammalian expression system The New England journal of medicine High 21675912
1996 Two vitamin D response elements (VDRE-1 at -150/-136 and VDRE-2 at -258/-244) in the rat CYP24 promoter act synergistically in response to 1,25(OH)2D3; VDR-RXR complex binds both VDREs but VDRE-2 shows higher VDR-RXR binding affinity while VDRE-1 shows greater transactivation. Transient transfection of native and mutant promoter-reporter constructs in multiple cell lines; gel mobility shift assays with VDR-RXR The Journal of biological chemistry High 8939905
2002 1,25-dihydroxyvitamin D3 induces CYP24 promoter activity via distinct ERK1/ERK2 and ERK5 MAP kinase modules in a Ras-dependent manner; ERK2 phosphorylates RXRα at S260 while ERK5 phosphorylates Ets-1 at T38, both required for full CYP24 transactivation, and an Ets-1 binding site cooperates with the proximal VDRE. Dominant-negative kinase mutants; pharmacological MAP kinase inhibitors; promoter-reporter assays; co-immunoprecipitation; in vitro phosphorylation assays; site-directed mutagenesis of phosphorylation sites The Journal of biological chemistry High 12048211
1998 PTH synergistically increases CYP24 mRNA levels and gene transcription in UMR106 osteoblastic cells when combined with 1,25(OH)2D3, acting through the cAMP signaling pathway; PTH also increases vitamin D receptor number at later timepoints. Northern blot for CYP24 mRNA; nuclear run-on transcription assay; CYP24 promoter-reporter transfection; 8-bromo-cAMP mimicry; PTH(3-34) negative control Endocrinology High 9681485
2005 The nuclear receptor PXR (pregnane X receptor) transactivates the human CYP24 promoter through the two proximal VDREs, leading to CYP24 mRNA upregulation and increased 24-hydroxylase activity in human hepatocytes; PXR agonists rifampicin and hyperforin induce CYP24 in vitro, and PCN/dexamethasone induce it in vivo in mice. Promoter-reporter transfection with PXR; chromatin analysis; 24-hydroxylase activity assay in human hepatocytes; in vivo measurement of 24,25(OH)2D3 in mice; RT-PCR The Journal of clinical investigation High 15630458
2005 Chromatin immunoprecipitation revealed spatio-temporal VDR binding to four distinct promoter regions of human CYP24 (including three novel upstream regions with VDRE-like sequences); VDR simultaneously associates with RXR, coactivators, mediator, and RNA polymerase II at these regions in a region-specific pattern over 300 minutes. Chromatin immunoprecipitation (ChIP) across 25 contiguous genomic regions; re-ChIP for simultaneous protein association; reporter gene assays; in silico/in vitro VDRE screening Journal of molecular biology High 15919092
2004 Calcitonin stimulates CYP24 promoter activity in kidney HEK-293 cells via PKA and PKC (including atypical PKCζ) and Ras signaling pathways, acting through a GC box (Sp1) at -114/-101 and a CCAAT box (NF-Y) at -62/-51; ERK1/2 is not required for calcitonin-mediated induction. Stable and transient transfection of CYP24 promoter-reporter constructs; pharmacological inhibitors (H89, calphostin C); dominant-negative kinase mutants; overexpression of Sp1 and NF-Y Journal of molecular endocrinology High 14765994
2005 Genistein directly inhibits CYP24 enzyme activity in a non-competitive manner at low doses (50-100 nM), extending the half-life of 1,25(OH)2D3 and amplifying VDR upregulation in DU145 prostate cancer cells. Direct CYP24 enzyme activity assay in mitochondrial preparations; RT-PCR for VDR mRNA; western blot for VDR protein; reporter gene assays Molecular and cellular endocrinology High 15955619
2007 CYP24 promoter is epigenetically silenced by hypermethylation of two CpG island regions at the 5' end in tumor-derived endothelial cells (TDEC) but not in normal endothelial cells; this prevents VDR recruitment and blocks calcitriol-induced CYP24 expression, contributing to selective calcitriol sensitivity in TDEC. Methylation-specific PCR and bisulfite sequencing; ChIP for VDR; 5-aza-2'-deoxycytidine treatment; CYP24 siRNA; CYP24 mRNA, protein, and enzymatic activity assays The Journal of biological chemistry High 17244627
2010 CYP24A1 expression in prostate cancer cells is repressed by promoter DNA methylation and repressive histone modifications (H3K9me2); treatment with 5-aza-2'-deoxycytidine or trichostatin A activates CYP24A1 expression and increases VDR recruitment to the promoter; TSA increases H3K9ac and H3K4me2 while decreasing H3K9me2. DNA methyltransferase inhibitor treatment; HDAC inhibitor treatment; bisulfite pyrosequencing; ChIP-qPCR for histone marks and VDR; RT-PCR; in vitro methylation of CYP24A1 promoter with luciferase reporter Cancer research High 20587525
2007 A sequence between -548 and -294 bp (containing three potential Sp1 sites) acts synergistically with the two proximal VDREs for vitamin D3-induced CYP24 expression; this distal region is required for full magnitude of induction. Deletion constructs of human CYP24 promoter with luciferase reporter assay in human fibroblasts Biochemical and biophysical research communications Medium 17475215
2010 Unliganded VDR represses basal CYP24 transcription in breast cancer cells; this repressive activity requires an intact VDR AF-1 domain (FokI polymorphism truncating VDR by 3 amino acids abolishes repression); VDR siRNA knockdown increases CYP24 expression. VDR overexpression and siRNA knockdown; CYP24 promoter-reporter assay; RT-PCR; western blot; nuclear fractionation/localization Molecular and cellular biochemistry Medium 20440542
2014 In dendritic cells, calcitriol-induced upregulation of CYP24A1 curtails vitamin D functional effects (limiting autocrine vitamin D activity), whereas this regulatory feedback is less effective in macrophages; DCs express a truncated CYP27B1 transcript reducing vitamin D activation. Comparison of 25(OH)D to 1,25(OH)2D conversion rates in DCs vs macrophages; RT-PCR for CYP24A1, CYP27B1; functional assays for vitamin D-responsive gene expression and DC maturation European journal of immunology Medium 24643654
2014 The TMPRSS2:ERG fusion gene synergizes with VDR to induce CYP24A1 expression, limiting intracellular 1,25D levels; TMPRSS2:ERG depletion substantially reduced 1,25D-mediated CYP24A1 induction in VCaP cells, and artificial expression synergized with 1,25D to greatly increase CYP24A1. siRNA depletion of TMPRSS2:ERG in VCaP cells; stable overexpression of TMPRSS2:ERG isoform in LNCaP cells; RT-PCR for CYP24A1; in vivo xenograft tumor growth with vitamin D analog Endocrinology Medium 24926821
2014 CYP24A1 mRNA is translationally upregulated under inflammatory conditions via an IRES element in the 5'UTR of cyp24a1; this IRES-dependent translation is activated by macrophage-conditioned medium and is sensitive to PI3K inhibition while constitutively active Akt suffices to induce IRES activity. Polysome profiling and microarray analysis; bicistronic reporter assays for IRES activity; PI3K inhibitor and constitutively active Akt overexpression PloS one Medium 24416388
2019 PTH suppresses Cyp24a1 expression in the kidney through a kidney-specific downstream enhancer (DS1); FGF23 induces Cyp24a1 through this DS1 enhancer and synergizes with 1,25(OH)2D3; deletion of Cyp24a1 enhancer elements in mice reduces 1,25(OH)2D3-dependent induction and eliminates intestinal Cyp24a1 induction. Mouse genomic enhancer deletion models; gene expression analysis in kidney and other tissues; hormone treatment experiments The Journal of steroid biochemistry and molecular biology High 31629064
2024 The proximal promoter VDREs (PRO VDREs) of Cyp24a1 are required for 1,25(OH)2D3-induced kidney expression and are essential for intestinal Cyp24a1 induction; FGF23 induction is reduced but not eliminated by PRO VDRE mutation; PTH suppression of Cyp24a1 is unchanged by PRO VDRE mutation, acting through the DS1 enhancer; PRO and DS enhancers act cooperatively. In vivo VDRE mutation in mouse by genome editing; ChIP for VDR; gene expression analysis after hormone treatment Endocrinology High 39363152
2019 Histone marks at the CYP24A1 promoter in osteoblastic cells switch from repressive (H4R3me2s deposited by PRMT5, with low H3/H4 acetylation) to active (increased H3/H4 acetylation, H3R17me2a by CARM1, H4R3me2a by PRMT1) upon 1,25(OH)2D3 treatment; VDR/SRC-1 complex is recruited and PRMT5 is released. ChIP-qPCR for multiple histone marks and chromatin-associated proteins; siRNA knockdown; VDR/SRC-1 co-immunoprecipitation implied by complex assembly data Journal of cellular physiology Medium 31868234
2021 CYP24A1 is solely responsible for conversion of 25(OH)D3 to 23,25(OH)2D3 via 23S,25(OH)2D3 in rats; CYP3A (not CYP24A1) converts 23,25,26(OH)3D3 to 25(OH)D3-26,23-lactone as shown using Cyp24a1 KO rats and recombinant human CYP species with ketoconazole inhibition. CRISPR/Cas9-generated Cyp24a1 KO rats; oral administration of 25(OH)D3 and metabolite intermediates; recombinant CYP enzyme studies; ketoconazole inhibition; LC/MS metabolite analysis The Journal of biological chemistry High 33865853
2004 CYP24 over-expression and CYP24 knockout (CYP24-XO) mouse studies showed CYP24 metabolizes both 25-OH-D3 and 1α,25-(OH)2D3 at similar in vitro rates, but DBP concentration strongly influences the rate for 25-OH-D3 but not 1α,25-(OH)2D3; CYP24-XO mice produce no measurable 24,25-(OH)2D3 after 25-OH-D3 administration. CYP24 overexpression system; CYP24 knockout mouse model; LC/MS and radioisotopic detection; in vivo and in vitro metabolite analysis The Journal of steroid biochemistry and molecular biology High 15225763
2015 Human CYP24A1 metabolizes 20(OH)D3 preferentially at C25 (while rat prefers C24), and metabolizes 20,23(OH)2D3 through multiple oxidations including C23-C24 bond cleavage analogous to the C24-oxidation pathway of 1,25(OH)2D3 catabolism. In vitro reconstituted enzyme assay with rat and human CYP24A1; NMR characterization; high-resolution mass spectrometry The Journal of steroid biochemistry and molecular biology High 25727742
2016 Progestins inhibit calcitriol-induced CYP24A1 expression in a progesterone receptor (PR)-dependent manner in ovarian and breast cancer cells; cells lacking PR do not show this inhibition; mouse ovaries showed significant reduction in CAL-induced Cyp24a1 mRNA and protein after progesterone treatment. RT-PCR and western blot for CYP24A1 in PR-expressing vs PR-negative cell lines; in vivo mouse ovary experiment; TUNEL apoptosis assay Gynecologic oncology Medium 27106018
2018 5α-dihydrotestosterone (DHT) reduces renal Cyp24a1 expression by suppressing progesterone receptor (Pgr), which has a progesterone receptor-binding site on the Cyp24a1 promoter; DHT-mediated Pgr reduction decreases transcriptional activation of Cyp24a1, increasing blood 25(OH)D3 levels. Orchidectomized mouse model with DHT treatment; RT-PCR and western blot for Pgr and Cyp24a1; ER-positive and ER-negative cell line analysis; promoter analysis Journal of molecular endocrinology Medium 29382742
2010 Valproic acid (VPA) enhances 1,25(OH)2D3-mediated CYP24 expression via activation of ERK (but not JNK or p38) and partly through HDAC1 inhibition; VPA potentiates VDR-mediated transactivation of the CYP24 promoter through a mechanism distinct from trichostatin A. CYP24 mRNA measurement in human hepatocytes and HEK293 cells; CYP24 promoter-reporter assays; MAPK inhibitors and activation analysis; comparison with TSA Toxicology letters Medium 21115105
2023 LSH (lymphoid-specific helicase) activates CYP24A1 transcription by binding its promoter, promoting nucleosome eviction, and reducing H3K27me3 occupancy; LSH is stabilized by USP11-mediated deubiquitination; erastin disrupts USP11-LSH interaction, leading to LSH ubiquitination and degradation, which reduces CYP24A1 and inhibits ferroptosis resistance in colorectal cancer cells. Co-immunoprecipitation for USP11-LSH interaction; ChIP for LSH binding at CYP24A1 promoter and H3K27me3; ubiquitination assays; CRC cell ferroptosis assays; siRNA knockdown Cell death & disease Medium 37414755
2021 SQLE promotes CRC cell proliferation through accumulation of calcitriol (active vitamin D3) and stimulation of CYP24A1-mediated MAPK signaling; SQLE inhibition reduces calcitriol and CYP24A1 levels, increases intracellular Ca2+, and suppresses MAPK signaling, inhibiting CRC growth. RNA sequencing; transcriptome and untargeted metabolomics; western blotting; siRNA knockdown; xenograft tumor models; SQLE inhibitor (terbinafine) treatment Cancer communications Medium 34268906
2021 miR-30b-5p directly targets CYP24A1 (validated by luciferase reporter assay) and negatively regulates its expression; CYP24A1 knockdown attenuates neuropathic pain and neuroinflammation; CYP24A1 promotes Wnt/β-catenin signaling in neuropathic pain context. Luciferase reporter assay for miRNA-target interaction; RT-qPCR and western blot; intrathecal miR-30b-5p delivery; behavioral pain assays; ELISA for cytokines Experimental brain research Medium 34748047
2019 Mammary-specific conditional knockout of Cyp24a1 reduces terminal end bud number, ductal outgrowth, and branching during puberty and alveologenesis in early pregnancy by inhibiting proliferation but not apoptosis in basal and luminal mammary epithelial cells; ablation also increases sensitivity to lower 1,25(OH)2D3 concentrations in vitro. Conditional (mammary-specific) Cyp24a1 knockout mouse model; histological analysis; BrdU proliferation and TUNEL apoptosis assays; in vitro cell treatment The Journal of steroid biochemistry and molecular biology High 30654105
2012 Increased CYP24A1 expression in diabetic kidney is driven by protein kinase C activation and H2O2 production, leading to cellular senescence followed by apoptosis in renal proximal tubules; this involves increased caspase-3 expression and activation. CYP24A1 expression analysis in diabetic rat kidneys; PKC inhibitor experiments; H2O2 manipulation; senescence and apoptosis assays; caspase-3 activity measurement PloS one Medium 23119081

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Mutations in CYP24A1 and idiopathic infantile hypercalcemia. The New England journal of medicine 452 21675912
2011 25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D. Archives of biochemistry and biophysics 387 22100522
2005 Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. The Journal of clinical investigation 231 15630458
2005 Expression of VDR and CYP24A1 mRNA in human tumors. Cancer chemotherapy and pharmacology 191 16180015
2006 Lack of the light-harvesting complex CP24 affects the structure and function of the grana membranes of higher plant chloroplasts. The Plant cell 190 17114352
2008 Minor antenna proteins CP24 and CP26 affect the interactions between photosystem II subunits and the electron transport rate in grana membranes of Arabidopsis. The Plant cell 175 18381925
2000 Dual metabolic pathway of 25-hydroxyvitamin D3 catalyzed by human CYP24. European journal of biochemistry 152 11012668
2012 Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies. American journal of physiology. Endocrinology and metabolism 121 22871339
2005 Spatio-temporal activation of chromatin on the human CYP24 gene promoter in the presence of 1alpha,25-Dihydroxyvitamin D3. Journal of molecular biology 118 15919092
2009 The candidate oncogene CYP24A1: A potential biomarker for colorectal tumorigenesis. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 111 19901270
1996 Transcriptional synergism between vitamin D-responsive elements in the rat 25-hydroxyvitamin D3 24-hydroxylase (CYP24) promoter. The Journal of biological chemistry 97 8939905
2013 1,25-(OH)2D-24 Hydroxylase (CYP24A1) Deficiency as a Cause of Nephrolithiasis. Clinical journal of the American Society of Nephrology : CJASN 95 23293122
2002 Role of MAP kinases in the 1,25-dihydroxyvitamin D3-induced transactivation of the rat cytochrome P450C24 (CYP24) promoter. Specific functions for ERK1/ERK2 and ERK5. The Journal of biological chemistry 92 12048211
2007 Comprehensive association analysis of the vitamin D pathway genes, VDR, CYP27B1, and CYP24A1, in prostate cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 91 17932346
2004 Clinical significance of the overexpression of the candidate oncogene CYP24 in esophageal cancer. Annals of oncology : official journal of the European Society for Medical Oncology 85 14760115
2010 Epigenetic regulation of vitamin D 24-hydroxylase/CYP24A1 in human prostate cancer. Cancer research 77 20587525
2005 Genistein potentiates the growth inhibitory effects of 1,25-dihydroxyvitamin D3 in DU145 human prostate cancer cells: role of the direct inhibition of CYP24 enzyme activity. Molecular and cellular endocrinology 71 15955619
2019 Mechanistic homeostasis of vitamin D metabolism in the kidney through reciprocal modulation of Cyp27b1 and Cyp24a1 expression. The Journal of steroid biochemistry and molecular biology 69 31629064
2011 CYP24A1 and kidney disease. Current opinion in nephrology and hypertension 67 21610497
2015 Successful treatment of hypercalcaemia associated with a CYP24A1 mutation with fluconazole. Clinical kidney journal 66 26251716
2006 1alpha,25-dihydroxyvitamin D3 downregulates CYP27B1 and induces CYP24A1 in colon cells. Molecular and cellular endocrinology 63 17029768
2013 Increased copy-number and not DNA hypomethylation causes overexpression of the candidate proto-oncogene CYP24A1 in colorectal cancer. International journal of cancer 61 23463632
2012 Expression of the vitamin D metabolizing enzyme CYP24A1 at the annulus of human spermatozoa may serve as a novel marker of semen quality. International journal of andrology 60 22404291
2007 Epigenetic silencing of CYP24 in tumor-derived endothelial cells contributes to selective growth inhibition by calcitriol. The Journal of biological chemistry 59 17244627
2010 Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification. Arteriosclerosis, thrombosis, and vascular biology 58 20847308
2013 DNA methylation levels of CYP2R1 and CYP24A1 predict vitamin D response variation. The Journal of steroid biochemistry and molecular biology 57 24128439
2009 Vitamin D related genes, CYP24A1 and CYP27B1, and colon cancer risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 56 19706847
2021 Squalene epoxidase promotes colorectal cancer cell proliferation through accumulating calcitriol and activating CYP24A1-mediated MAPK signaling. Cancer communications (London, England) 55 34268906
2019 Acidosis enhances the self-renewal and mitochondrial respiration of stem cell-like glioma cells through CYP24A1-mediated reduction of vitamin D. Cell death & disease 55 30631035
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