Cyp24a1

Summary

Gene Symbol: Cyp24a1
Description: cytochrome P450, family 24, subfamily a, polypeptide 1
Alias: 24-OHase, CP24, Cyp24, 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial, 25-hydroxyvitamin D-24-hydroxylase, cytochrome P450 24A1, cytochrome P450, 24, cytochrome P450, 24a1, cytochrome P450-CC24, vitamin D(3) 24-hydroxylase
Species: mouse
Products:     Cyp24a1

Top Publications

  1. Muindi J, Yu W, Ma Y, Engler K, Kong R, Trump D, et al. CYP24A1 inhibition enhances the antitumor activity of calcitriol. Endocrinology. 2010;151:4301-12 pubmed publisher
    ..Therefore, we investigated whether the inhibition of 24-hydroxylase (CYP24A1), the major calcitriol inactivating enzyme, by ketoconazole (KTZ) or RC2204 modulates calcitriol serum ..
  2. St Arnaud R. CYP24A1-deficient mice as a tool to uncover a biological activity for vitamin D metabolites hydroxylated at position 24. J Steroid Biochem Mol Biol. 2010;121:254-6 pubmed publisher
    The CYP24A1 enzyme (25-hydroxyvitamin D-24-hydroxylase) not only is involved in the catabolic breakdown of 1,25-dihydroxyvitamin D [1,25(OH)2D] but also generates the 24,25-dihydroxyvitamin D [24,25(OH)2D] metabolite...
  3. Akeno N, Saikatsu S, Kawane T, Horiuchi N. Mouse vitamin D-24-hydroxylase: molecular cloning, tissue distribution, and transcriptional regulation by 1alpha,25-dihydroxyvitamin D3. Endocrinology. 1997;138:2233-40 pubmed
  4. Bai X, Miao D, Xiao S, Qiu D, St Arnaud R, Petkovich M, et al. CYP24 inhibition as a therapeutic target in FGF23-mediated renal phosphate wasting disorders. J Clin Invest. 2016;126:667-80 pubmed publisher
    b>CYP24A1 (hereafter referred to as CYP24) enzymatic activity is pivotal in the inactivation of vitamin D metabolites. Basal renal and extrarenal CYP24 is usually low but is highly induced by its substrate 1,25-dihydroxyvitamin D...
  5. Ewart Toland A, Briassouli P, de Koning J, Mao J, Yuan J, Chan F, et al. Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human. Nat Genet. 2003;34:403-12 pubmed
    ..This interaction results in colocalization of UBE2N with STK15 at the centrosomes during mitosis. These results are consistent with an important role for the Ile31 variant of STK15 in human cancer susceptibility. ..
  6. Itoh S, Yoshimura T, Iemura O, Yamada E, Tsujikawa K, Kohama Y, et al. Molecular cloning of 25-hydroxyvitamin D-3 24-hydroxylase (Cyp-24) from mouse kidney: its inducibility by vitamin D-3. Biochim Biophys Acta. 1995;1264:26-8 pubmed
    ..1 and 94.7% amino acid identity with human and rat CYP24s, respectively. Among mouse organs examined, Cyp-24 mRNA could be detected in the kidney. When mice were treated with vitamin D-3, Cyp-24 mRNA was induced in the kidney. ..
  7. Lieben L, Stockmans I, Moermans K, Carmeliet G. Maternal hypervitaminosis D reduces fetal bone mass and mineral acquisition and leads to neonatal lethality. Bone. 2013;57:123-31 pubmed publisher
    ..In conclusion, these data indicate that high maternal 1,25(OH)2D levels are transferred across the placental barrier and adversely affect the total amount of calcium stored in fetal bones which is accompanied by neonatal death. ..
  8. Malas S, Peters J, Abbott C. The genes for endothelin 3, vitamin D 24-hydroxylase, and melanocortin 3 receptor map to distal mouse chromosome 2, in the region of conserved synteny with human chromosome 20. Mamm Genome. 1994;5:577-9 pubmed
  9. Roy S, Martel J, Tenenhouse H. Growth hormone normalizes renal 1,25-dihydroxyvitamin D3-24-hydroxylase gene expression but not Na+-phosphate cotransporter (Npt2) mRNA in phosphate-deprived Hyp mice. J Bone Miner Res. 1997;12:1672-80 pubmed

More Information

Publications34

  1. St Arnaud R. Targeted inactivation of vitamin D hydroxylases in mice. Bone. 1999;25:127-9 pubmed
    ..The phenotype of the second generation 24-OHase-null mice also suggests a key role for 24,25(OH)2D in intramembranous bone formation during development. ..
  2. Kaufmann M, Lee S, Pike J, Jones G. A High-Calcium and Phosphate Rescue Diet and VDR-Expressing Transgenes Normalize Serum Vitamin D Metabolite Profiles and Renal Cyp27b1 and Cyp24a1 Expression in VDR Null Mice. Endocrinology. 2015;156:4388-97 pubmed publisher
    ..b>CYP24A1 is a cytochrome P450 enzyme that is involved in the side chain oxidation and destruction of both 1,25(OH)2D3 and ..
  3. Chung I, Karpf A, Muindi J, Conroy J, Nowak N, Johnson C, et al. Epigenetic silencing of CYP24 in tumor-derived endothelial cells contributes to selective growth inhibition by calcitriol. J Biol Chem. 2007;282:8704-14 pubmed
    ..vitamin D receptor-signaling axis, this study demonstrates that upon treatment with calcitriol, 24-hydroxylase (CYP24) mRNA, protein and enzymatic activity were markedly induced in MDEC in a time-dependent manner but not in TDEC...
  4. Zhou C, Assem M, Tay J, Watkins P, Blumberg B, Schuetz E, et al. Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia. J Clin Invest. 2006;116:1703-12 pubmed
    ..Cytochrome P450, family 24-mediated (CYP24-mediated) 24-hydroxylation of 1,25(OH)2D3 is an important step in the catabolism of 1,25(OH)2D3...
  5. Pascussi J, Robert A, Nguyen M, Walrant Debray O, Garabedian M, Martin P, et al. Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest. 2005;115:177-86 pubmed
    ..Here we show that these drugs lead to the upregulation of 25-hydroxyvitamin D(3)-24-hydroxylase (CYP24) gene expression through the activation of the nuclear receptor pregnane X receptor (PXR; NR1I2)...
  6. Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K, Nabeshima Y. Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Mol Endocrinol. 2003;17:2393-403 pubmed
    ..These observations suggest that klotho may participate in a negative regulatory circuit of the vitamin D endocrine system, through the regulation of 1alpha-hydroxylase gene expression...
  7. Zhang Y, Wu S, Gu S, Lv F. Changes of renal vitamin D metabolic enzyme expression and calcium transporter abundance in obstructive nephropathy. Nephrology (Carlton). 2011;16:710-4 pubmed publisher
  8. Masuda S, Byford V, Arabian A, Sakai Y, Demay M, St Arnaud R, et al. Altered pharmacokinetics of 1alpha,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 in the blood and tissues of the 25-hydroxyvitamin D-24-hydroxylase (Cyp24a1) null mouse. Endocrinology. 2005;146:825-34 pubmed
    The 25-hydroxyvitamin D-24-hydroxylase (CYP24A1) plays an important role in regulating concentrations of both the precursor 25-hydroxyvitamin D3 [25(OH)D3] and the hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)(2)D3]...
  9. Masuda S, Kaufmann M, Byford V, Gao M, St Arnaud R, Arabian A, et al. Insights into Vitamin D metabolism using cyp24 over-expression and knockout systems in conjunction with liquid chromatography/mass spectrometry (LC/MS). J Steroid Biochem Mol Biol. 2004;89-90:149-53 pubmed
    ..Our studies focused on: (1) elucidating the role of CYP24 in 25-OH-D3 and 1alpha,25-(OH)2D3 metabolism; (2) exploring how DBP influences this process; (3) measuring 25-OH-..
  10. Chau H, El Maadawy S, McKee M, Tenenhouse H. Renal calcification in mice homozygous for the disrupted type IIa Na/Pi cotransporter gene Npt2. J Bone Miner Res. 2003;18:644-57 pubmed
    ..In summary, we show that Npt2 gene ablation is associated with renal calcification and suggest that mutations in the NPT2 gene may contribute to nephrocalcinosis in a subset of patients with familial hypercalciuria. ..
  11. Roy S, Tenenhouse H. Transcriptional regulation and renal localization of 1,25-dihydroxyvitamin D3-24-hydroxylase gene expression: effects of the Hyp mutation and 1,25-dihydroxyvitamin D3. Endocrinology. 1996;137:2938-46 pubmed
  12. Azam N, Zhang M, Wang X, Tenenhouse H, Portale A. Disordered regulation of renal 25-hydroxyvitamin D-1alpha-hydroxylase gene expression by phosphorus in X-linked hypophosphatemic (hyp) mice. Endocrinology. 2003;144:3463-8 pubmed
    ..The present findings demonstrate that regulation of both the p450c1alpha and p45024 genes by phosphorus is disordered in Hyp mice at the level of renal 1alpha-hydroxylase activity and renal p450c1alpha and p450c24 mRNA expression. ..
  13. Shannon M, Richardson L, Christian A, Handel M, Thelen M. Differential gene expression of mammalian SPO11/TOP6A homologs during meiosis. FEBS Lett. 1999;462:329-34 pubmed
    ..2-13.3, a region that is amplified in some breast cancers. Sequence homology and differential expression together support a highly conserved role for SPO11 in the enzymatic cleavage of DNA that accompanies meiotic recombination. ..
  14. Pike J, Meyer M. Regulation of mouse Cyp24a1 expression via promoter-proximal and downstream-distal enhancers highlights new concepts of 1,25-dihydroxyvitamin D(3) action. Arch Biochem Biophys. 2012;523:2-8 pubmed publisher
    b>CYP24A1 functions in vitamin D target tissues to degrade 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))...
  15. Masuda S, Strugnell S, Knutson J, St Arnaud R, Jones G. Evidence for the activation of 1alpha-hydroxyvitamin D2 by 25-hydroxyvitamin D-24-hydroxylase: delineation of pathways involving 1alpha,24-dihydroxyvitamin D2 and 1alpha,25-dihydroxyvitamin D2. Biochim Biophys Acta. 2006;1761:221-34 pubmed
    ..We used keratinocytes and recombinant human enzyme to test if the 25-hydroxyvitamin D-24-hydroxylase (CYP24A1) is capable of target cell activation and inactivation of a model prodrug, 1alpha-hydroxyvitamin D2 (1alpha(OH)D2)..
  16. Zhu Y, He Q, Aydin C, Rubera I, Tauc M, Chen M, et al. Ablation of the Stimulatory G Protein α-Subunit in Renal Proximal Tubules Leads to Parathyroid Hormone-Resistance With Increased Renal Cyp24a1 mRNA Abundance and Reduced Serum 1,25-Dihydroxyvitamin D. Endocrinology. 2016;157:497-507 pubmed publisher
    ..05). Our findings indicate that Gsα is required in PTs for suppressing renal vitamin D 24-hydroxylase mRNA levels and for maintaining normal serum 1,25(OH)2D. ..
  17. Husseini A, St Arnaud R. CYP24A1-deficiency does not affect bone regeneration in distraction osteogenesis. J Steroid Biochem Mol Biol. 2017;173:168-172 pubmed publisher
    ..Our laboratory has generated a mouse model deficient for the Cyp24a1 gene for studying the role of 24,25-(OH)2D...
  18. Zou M, Baitei E, BinEssa H, Al Mohanna F, Parhar R, St Arnaud R, et al. Cyp24a1 Attenuation Limits Progression of BrafV600E -Induced Papillary Thyroid Cancer Cells and Sensitizes Them to BRAFV600E Inhibitor PLX4720. Cancer Res. 2017;77:2161-2172 pubmed publisher
    b>CYP24A1, the primary inactivating enzyme for vitamin D, is often overexpressed in human cancers, potentially neutralizing the antitumor effects of calcitriol, the active form of vitamin D...
  19. Zhang Z, Li B, Shi Y, Tong J. [The effects of serum calcium and 1 alpha hydroxylase on the expression of 24-hydroxylase gene]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2006;22:339-42 pubmed
    ..There are no direct interaction between 1 alpha-hydroxylase gene and 24-hydroxylase gene. ..
  20. Valrance M, Brunet A, Acosta A, Welsh J. Dissociation of growth arrest and CYP24 induction by VDR ligands in mammary tumor cells. J Cell Biochem. 2007;101:1505-19 pubmed
    ..analog EB1089 induce growth arrest and transcriptionally upregulate the well-characterized VDR target gene CYP24. 1,25D also induces apoptosis in WT145 cells through activation of initiator and executioner caspases and the ..
  21. Jones G, Tenenhouse H. 1,25(OH)2D, the preferred substrate for CYP24. J Bone Miner Res. 2002;17:179-81 pubmed
  22. St Arnaud R, Arabian A, Travers R, Barletta F, Raval Pandya M, Chapin K, et al. Deficient mineralization of intramembranous bone in vitamin D-24-hydroxylase-ablated mice is due to elevated 1,25-dihydroxyvitamin D and not to the absence of 24,25-dihydroxyvitamin D. Endocrinology. 2000;141:2658-66 pubmed
    ..Our results confirm the physiological importance of the 24-OHase enzyme for maintaining vitamin D homeostasis, and they reveal that 24,25-dihydroxyvitamin D is a dispensable metabolite during bone development. ..
  23. Williamson C, Dutton E, Abbott C, Beechey C, Ball S, Peters J. Thirteen genes (Cebpb, E2f1, Tcf4, Cyp24, Pck1, Acra4, Edn3, Kcnb1, Mc3r, Ntsr, Cd40, Plcg1 and Rcad) that probably lie in the distal imprinting region of mouse chromosome 2 are not monoallelically expressed. Genet Res. 1995;65:83-93 pubmed
    ..These included 3 genes (Cebpb, E2f1 and Tcf4) that express transcription factors, 2 genes (Cyp24 and Pck1) that are involved in growth, 5 genes (Acra4, Edn3, Kcnb1, Mc3r and Ntsr) where a defect could lead to ..
  24. Tourigny A, Charbonneau F, Xing P, Boukrab R, Rousseau G, St Arnaud R, et al. CYP24A1 exacerbated activity during diabetes contributes to kidney tubular apoptosis via caspase-3 increased expression and activation. PLoS ONE. 2012;7:e48652 pubmed publisher
    ..Previous studies have also shown that CYP24A1 (an enzyme implicated in vitamin D metabolism), might play an important role in furthering the progression of ..
  25. Ohata Y, Yamazaki M, Kawai M, Tsugawa N, Tachikawa K, Koinuma T, et al. Elevated fibroblast growth factor 23 exerts its effects on placenta and regulates vitamin D metabolism in pregnancy of Hyp mice. J Bone Miner Res. 2014;29:1627-38 pubmed publisher
    ..We analyzed the placental gene expression and found that the expression of Cyp24a1 encoding 25OHD-24-hydroxylase, a target gene for FGF23 in the kidney, was increased in the placentas of fetuses ..