Affinage

CYP17A1

Steroid 17-alpha-hydroxylase/17,20 lyase · UniProt P05093

Length
508 aa
Mass
57.4 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CYP17A1 is a bifunctional cytochrome P450 enzyme that catalyzes both steroid 17α-hydroxylation (essential for cortisol synthesis) and 17,20-lyase C–C bond cleavage (essential for androgen and sex steroid synthesis) within a single active site, using mechanistically distinct reactive intermediates: a compound I ferryl species for hydroxylation (requiring Thr306-mediated proton delivery) and a nucleophilic iron-peroxo anion for the lyase reaction (PMID:24299954, PMID:9892022). The ratio of these two activities is controlled post-translationally by serine phosphorylation (via a ROCK-primed, p38α-mediated pathway opposed by PP2A/SET) and by allosteric interaction with cytochrome b5, whose acidic residues Glu-48/Glu-49 contact CYP17A1 basic residues Arg-347/Arg-358/Lys-88 to enhance electron transfer from P450 oxidoreductase selectively for the lyase reaction (PMID:25315771, PMID:15687493, PMID:12444089, PMID:18187541, PMID:30682387). Transcription is activated by SF-1, GATA-4/6–Sp1 complexes, and Pbx1 at the proximal promoter in a cAMP-dependent and tissue-specific manner, modulated by SF-1 lipid ligands (sphingosine and phosphatidic acid), and repressed by glucocorticoid receptor, androgen receptor, and promoter DNA methylation (PMID:14988427, PMID:9178749, PMID:16887917, PMID:17664281, PMID:8385739). Homozygous deletion in mice causes embryonic lethality before gastrulation, with CYP17A1 protein localizing to embryonic endoderm at E7, indicating an essential early developmental role that cannot be rescued by downstream steroid supplementation (PMID:15169901).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1993 Medium

    Establishing that glucocorticoid receptor-mediated transcriptional repression of CYP17 explained the negative feedback of cortisol on adrenal androgen and cortisol precursor synthesis, defining a key hormonal regulatory axis.

    Evidence CYP17-CAT reporter and endogenous mRNA analysis in bovine adrenocortical cells with dexamethasone and GR antagonist RU-486

    PMID:8385739

    Open questions at the time
    • GR binding site on the CYP17 promoter not precisely mapped
    • mechanism of GR trans-repression (tethering vs. direct DNA binding) not resolved
  2. 1994 Medium

    Early structure–function mapping identified active-site residues G111 and G301 as essential for both catalytic activities, and the homeodomain protein Pbx1 was identified as a cAMP-responsive transcriptional activator at the CRS1 element, establishing that CYP17 transcription involves non-classical transcription factors.

    Evidence Homology modeling on P450cam plus site-directed mutagenesis with COS-1 activity assays; CRS1 affinity purification with protein microsequencing and reporter assays

    PMID:7913464 PMID:8015556

    Open questions at the time
    • Active-site model based on distant P450cam homolog, not a CYP17A1 crystal structure
    • Pbx1 role not confirmed by loss-of-function in steroidogenic cells
  3. 1997 Medium

    A complex regulatory logic was revealed at the CYP17 promoter involving cooperative activation by SF-1 with novel factors (StF-IT-2), repression by COUP-TF displaced by NGFI-B, and androgen receptor-mediated repression requiring AR DNA binding to the cAMP-responsive region, establishing multi-factorial transcriptional integration.

    Evidence EMSA, DNase I footprinting, and deletion/mutation reporter assays in Leydig and adrenal cell lines with cotransfected receptors

    PMID:8994191 PMID:9178749

    Open questions at the time
    • Identity of StF-IT-1 and StF-IT-2 not molecularly characterized
    • AR repression mechanism (competition vs. squelching) not fully resolved
    • In vivo chromatin occupancy not tested
  4. 1999 High

    The molecular basis for selective 17,20-lyase deficiency was established: R347H and R358Q mutations disrupt redox-partner interaction rather than substrate binding, proving the two catalytic activities are governed by structurally separable domains.

    Evidence Yeast microsome reconstitution with systematic variation of POR and cytochrome b5; kinetic analysis; COS-1 cell transfection

    PMID:12466376 PMID:9892022

    Open questions at the time
    • No crystal structure of CYP17A1 available at this time to visualize the interaction surface
    • Quantitative contribution of each residue to electron transfer not measured
  5. 2002 High

    Post-translational regulation of lyase-to-hydroxylase ratio was defined: PP2A directly dephosphorylates CYP17A1 to suppress lyase activity, counteracted by the PP2A inhibitor SET, and a cAMP→PKA→MKP-1⊣ERK pathway modulates SF-1 phosphorylation state to control CYP17 transcription.

    Evidence Co-IP of PP2A with P450c17; siRNA and pharmacological PP2A inhibition with steroid readout; in vitro PKA phosphorylation of MKP-1; antisense and siRNA functional assays

    PMID:12444089 PMID:12506119

    Open questions at the time
    • Specific serine residue(s) dephosphorylated by PP2A on CYP17A1 not identified
    • SET mechanism of action in adrenal cells not fully dissected
  6. 2004 High

    GATA-4/6–Sp1 interaction was shown to activate CYP17A1 transcription at the proximal promoter, co-localization of CYP17A1 and cytochrome b5 was mapped to androgen-producing tissues in vivo, and CYP17A1 knockout mice were shown to be embryonic lethal before gastrulation with enzyme activity rising sharply at E6–E7.

    Evidence ChIP, Co-IP, GST pull-down, and reporter assays for GATA/Sp1; immunohistochemistry in human steroidogenic tissues; gene knockout in mice with enzyme activity assays and steroid rescue attempts

    PMID:14985252 PMID:14988427 PMID:15169901

    Open questions at the time
    • Essential CYP17A1 product in early embryogenesis not identified (DHEA rescue failed)
    • Whether GATA-4/6 are required in vivo for CYP17A1 expression not tested by conditional knockout
  7. 2005 High

    Phosphorylation and cytochrome b5 were shown to independently and non-additively enhance 17,20-lyase activity, both converging on improved POR interaction, resolving how the two post-translational regulators integrate.

    Evidence RNAi of cytochrome b5 in NCI-H295A cells plus purified phosphorylated/unphosphorylated enzyme reconstitution

    PMID:15687493

    Open questions at the time
    • Identity of the direct kinase phosphorylating CYP17A1 not yet established
    • Whether phosphorylation and b5 share the identical interaction surface on POR unknown
  8. 2007 Medium

    SF-1 lipid ligands were identified as functional switches: sphingosine represses and phosphatidic acid (produced by nuclear DGKθ upon ACTH/cAMP stimulation) activates CYP17 transcription, revealing a lipid-signaling layer controlling steroidogenic gene expression.

    Evidence MS identification of SF-1-bound lipids; siRNA of ceramidases and DGKθ; ChIP for SF-1 at CYP17 promoter; reporter assays

    PMID:16887917 PMID:17664281

    Open questions at the time
    • Structural basis for SPH vs. PA switching of SF-1 conformation not determined
    • In vivo relevance of lipid-SF-1 regulation of CYP17A1 not tested
  9. 2008 Medium

    The ROCK/Rho pathway was placed upstream of the CYP17A1-phosphorylating kinase cascade, with ROCK1 acting as a priming kinase whose phosphorylation alone was insufficient, while GATA4 was confirmed as a direct activator of CYP17A1 in embryonic endoderm linking transcription to embryonic lethality.

    Evidence Kinase inhibitor panel and in vitro ROCK1 phosphorylation assay; ChIP for GATA4 at cyp17 promoter in F9 differentiated cells with siRNA knockdown

    PMID:18187541 PMID:18832096

    Open questions at the time
    • Direct kinase downstream of ROCK that phosphorylates CYP17A1 on functional serine(s) not identified at this point
    • Whether GATA4 loss explains embryonic lethality not tested
  10. 2014 High

    The cytochrome b5–CYP17A1 interaction interface was mapped at residue-level resolution (b5 E48/E49 contacting CYP17A1 R347/R358/K88), providing the first structural model of the complex and explaining the electrostatic basis for selective lyase stimulation.

    Evidence Zero-length cross-linking with mass spectrometric identification of inter-protein contacts; site-directed mutagenesis; crystal-structure-based protein docking

    PMID:25315771

    Open questions at the time
    • No experimentally determined co-crystal structure of the complex
    • Whether phosphorylation alters the b5 binding interface not tested
  11. 2015 High

    The mechanism by which cytochrome b5 stimulates lyase activity was shown to be allosteric modulation of electron-transfer kinetics rather than direct electron donation, resolved by biophysical measurements in reconstituted membrane systems.

    Evidence FRET in living cells; quartz crystal microbalance for protein–protein interaction; protein film voltammetry comparing wild-type and E48G/E49G mutant b5

    PMID:26587646

    Open questions at the time
    • Whether allosteric effect changes CYP17A1 conformation or POR docking geometry not determined
    • Kinetic parameters under native membrane lipid composition not measured
  12. 2019 Medium

    p38α (MAPK14) was identified as a direct kinase phosphorylating CYP17A1 under oxidative stress to selectively enhance lyase activity and DHEA production, partially resolving the long-standing question of kinase identity downstream of ROCK.

    Evidence p38α pharmacological inhibition and siRNA knockdown in NCI-H295A cells with LC-MS/MS steroid quantification after oxidant challenge

    PMID:30682387

    Open questions at the time
    • Specific phosphorylation site(s) targeted by p38α on CYP17A1 not mapped
    • Whether p38α is the sole direct kinase or one of several remains unclear
    • Relationship between p38α and ROCK pathway not directly tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the identity of the essential CYP17A1 product(s) required for pre-gastrulation embryonic development; the specific serine residue(s) phosphorylated to regulate lyase activity; whether p38α and ROCK converge on the same or distinct sites; and an experimentally determined co-crystal structure of the CYP17A1–cytochrome b5–POR ternary complex.
  • No co-crystal structure of CYP17A1–b5–POR complex
  • Essential embryonic substrate/product unidentified
  • Phosphosite mapping incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 5 GO:0016829 lyase activity 4
Localization
GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1430728 Metabolism 7 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-162582 Signal Transduction 6
Partners
CYB5AGATA4PORPP2ASAR1ASF1SP1

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 P450c17 mutations R347H and R358Q selectively destroy 17,20-lyase activity while preserving 17α-hydroxylase activity by disrupting the interaction of P450c17 with its electron-donating redox partners P450 oxidoreductase (OR) and cytochrome b5, not by affecting the substrate-binding active site. Cytochrome b5 at 30:1 molar excess partially restored lyase activity, and competitive inhibition experiments confirmed the active site was unaffected. Yeast microsome expression system with systematic variation of OR and cytochrome b5, enzyme kinetics (Km determination), competitive inhibition assays, COS-1 cell transfection Molecular endocrinology (Baltimore, Md.) High 9892022
2005 Serine phosphorylation of P450c17 and cytochrome b5 independently increase 17,20-lyase activity, both likely by enhancing the interaction between P450c17 and NADPH-cytochrome P450 oxidoreductase. RNAi suppression of cytochrome b5 in NCI-H295A cells reduced lyase activity by 30% without affecting 17α-hydroxylase; increased phosphorylation compensated for reduced b5. Using purified bacterial-expressed enzyme, either b5 or phosphorylation was required for lyase activity, but the two effects were non-additive. RNAi knockdown in human NCI-H295A adrenal cells; purified enzyme reconstitution with phosphorylated vs. unphosphorylated P450c17; in vitro steroid product assays The Journal of biological chemistry High 15687493
2002 Protein phosphatase 2A (PP2A) directly associates with P450c17 (co-immunoprecipitation) and dephosphorylates it, selectively reducing 17,20-lyase activity without affecting 17α-hydroxylase activity. PP2A inhibition by okadaic acid, fostriecin, or siRNA increased lyase activity. The phosphoprotein SET, found in adrenals, inhibits PP2A and thereby sustains lyase activity. Co-immunoprecipitation of PP2A with P450c17; siRNA knockdown of PP2A; phosphatase inhibitor treatment of NCI-H295A cells; steroid product measurement The Journal of biological chemistry High 12444089
2014 Electrostatic interactions between acidic residues Glu-48/Glu-49 of cytochrome b5 and basic residues Arg-347/Arg-358/Lys-88 of CYP17A1 are essential for stimulating 17,20-lyase activity. Zero-length cross-linking identified two specific inter-protein contact sites, and protein docking using crystal structures yielded a structural model of the CYP17A1–cytochrome b5 complex. Site-directed mutagenesis of cytochrome b5; zero-length chemical cross-linking (EDC); mass spectrometric identification of cross-linked peptide pairs; protein–protein docking based on crystal structures The Journal of biological chemistry High 25315771
2013 The Thr306 acid/alcohol residue of CYP17A1 is essential for efficient proton delivery and compound I formation during 17α-hydroxylase activity, but is dispensable for 17,20-lyase (carbon–carbon bond cleavage) activity, supporting a nucleophilic iron-peroxo anion (rather than compound I) as the reactive intermediate for the lyase reaction. T306A site-directed mutagenesis; Nanodisc reconstitution with P450 oxidoreductase; NADPH coupling efficiency assays; substrate turnover measurement for pregnenolone and progesterone Biochemical and biophysical research communications High 24299954
2002 CYP17 mutations in the steroid-binding domain (F114V, D116V) cause combined 17α-hydroxylase and 17,20-lyase deficiency, while mutations in the redox partner interaction domain (R347C, R347H) cause selective 17,20-lyase deficiency with near-normal 17α-hydroxylase, confirming that these are structurally and functionally separable domains. COS-1 cell transfection with mutant CYP17 constructs; steroid product measurement using multiple substrates (pregnenolone, progesterone, 17α-hydroxylated products) The Journal of clinical endocrinology and metabolism High 12466376
2008 ROCK (Rho-associated coiled-coil containing protein kinase)/Rho pathway members act upstream of the kinase that phosphorylates P450c17 and augments 17,20-lyase activity. ROCK1 phosphorylated P450c17 in vitro, but that phosphorylation alone did not increase lyase activity, placing ROCK upstream as a priming kinase. PKA, PI3K/Akt, and Ca2+/calmodulin/MAPK pathways were excluded by inhibitor panel. Kinase inhibitor panel; microarray of kinase expression in NCI-H295A cells; in vitro phosphorylation assay with ROCK1; COS-1 cell transfection; 17,20-lyase/17α-hydroxylase ratio measurement Endocrinology Medium 18187541
2019 Oxidative stress activates p38α (MAPK14), which phosphorylates P450c17 and selectively enhances 17,20-lyase activity and DHEA production without proportionately increasing 17α-hydroxylase activity. p38α inhibition and siRNA knockdown both attenuated oxidant-induced DHEA production in NCI-H295A cells. Oxidant treatment (palmitate, H2O2, HNE) of NCI-H295A cells; p38α pharmacological inhibition; siRNA knockdown; LC-MS/MS steroid measurement Molecular and cellular endocrinology Medium 30682387
2015 Cytochrome b5 alters the kinetics of electron transfer to CYP17A1 through allosteric protein–protein interaction; FRET in living cells confirmed close proximity; quartz crystal microbalance showed specific protein–protein interaction in a lipid membrane; voltammetry showed that wild-type b5 but not E48G/E49G mutant altered electron-transfer kinetics from electrode to P450c17. FRET in living cells; in silico docking; quartz crystal microbalance; protein film voltammetry with wild-type and mutant cytochrome b5 PloS one High 26587646
1997 Multiple orphan nuclear receptors regulate rat P450c17 gene transcription: SF-1 binds two distinct DNA regions; COUP-TF acts as a transcriptional repressor; NGFI-B can displace COUP-TF; newly identified factors StF-IT-1 and StF-IT-2 bind distinct upstream elements. SF-1 and NGFI-B increase transcription only when interacting with another DNA-bound protein (StF-IT-2), revealing a novel cooperative mechanism for orphan nuclear receptor action. 5'-deletion reporter assays in Leydig/adrenal cells; EMSA; DNase I footprinting; cotransfection with receptor expression vectors Molecular endocrinology (Baltimore, Md.) Medium 9178749
2004 GATA-4 and GATA-6 activate transcription of the human P450c17 gene by directly interacting with Sp1 (not Sp3) at the Sp1/Sp3 binding site in the proximal promoter. GST pull-down and co-immunoprecipitation demonstrated GATA-4/6–Sp1 interaction; ChIP confirmed this interaction occurs at the Sp1 site in the P450c17 promoter in NCI-H295A cells. DNA methylation silences CYP17A1, GATA-4, and GATA-6 in placental JEG-3 cells. GST pull-down; co-immunoprecipitation; chromatin immunoprecipitation (ChIP); promoter reporter assays; 5-aza-2-deoxycytidine demethylation; EMSA; DNase I footprinting Molecular endocrinology (Baltimore, Md.) High 14988427
2006 Sphingosine (SPH) is an endogenous ligand for steroidogenic factor-1 (SF-1) that negatively regulates CYP17 transcription. Tandem mass spectrometry showed SF-1 is bound to SPH and lyso-sphingomyelin under basal conditions; cAMP stimulation reduces bound SPH. siRNA silencing of ceramidases (which produce SPH) increased CYP17 mRNA, and SPH antagonized cAMP/SRC-1-stimulated CYP17 reporter activity. Tandem mass spectrometry of SF-1-bound lipids; siRNA knockdown of ceramidases; promoter reporter assays; SF-1 ligand-binding analysis Endocrinology Medium 16887917
2007 Phosphatidic acid (PA) produced by nuclear diacylglycerol kinase-theta (DGK-θ) binds SF-1 and promotes SF-1-dependent CYP17 transcription. ACTH/cAMP stimulation rapidly increases nuclear DGK activity and PA production. DGK-θ interacts directly with SF-1 via LXXLL motifs. DGK-θ siRNA knockdown inhibited cAMP-dependent CYP17 transcription and SF-1 binding to the CYP17 promoter. Tandem mass spectrometry of SF-1-bound lipids; nuclear DGK activity assay; siRNA knockdown of DGK-θ; ChIP for SF-1 at CYP17 promoter; reporter assays Molecular and cellular biology Medium 17664281
2002 cAMP-activated PKA phosphorylates MKP-1 (a nuclear dual-specificity phosphatase), which in turn dephosphorylates and inactivates ERK1/2; this shifts the phosphorylation state of SF-1 toward a transcriptionally active form, enhancing CYP17 transcription. MKP-1 antisense oligonucleotides attenuated cAMP-stimulated CYP17 expression; ERK1/2 siRNA increased CYP17 expression. In vitro PKA phosphorylation of MKP-1-GST fusion; 32P metabolic labeling and immunoprecipitation of MKP-1; antisense oligonucleotide silencing; promoter reporter assays; siRNA of ERK1/2 The Journal of biological chemistry Medium 12506119
1995 TNF-α inhibits cAMP-stimulated Cyp17 (P450c17) gene transcription in Leydig cells via a protein kinase C (PKC)-dependent mechanism. PKC activator PMA mimicked TNF-α inhibition; PKC inhibitor calphostin C fully reversed TNF-α inhibition of Cyp17-CAT reporter activity and P450c17 mRNA/protein. TNF-α promoted nuclear translocation of PKC-α. Primary mouse Leydig cell culture; Cyp17-CAT reporter transfection in MA-10 Leydig cells; PKC inhibitor/activator pharmacology; Western blot; indirect immunofluorescence of PKC-α translocation Endocrinology Medium 7628389
1997 Androgens repress cAMP-induced Cyp17 expression via the androgen receptor (AR) binding to sequences between -330 and -278 bp of the mouse Cyp17 promoter, overlapping the cAMP-responsive region (-346 to -245 bp). AR DNA-binding domain mutant lacking the second zinc finger failed to repress, demonstrating that DNA binding is required. The mechanism involves AR interference with proteins mediating cAMP induction. Cotransfection of Cyp17-CAT reporter with AR expression plasmids (wild-type and zinc-finger mutant) in MA-10 Leydig cells; 5'-deletion analysis; DNase I footprinting Molecular endocrinology (Baltimore, Md.) Medium 8994191
1994 The homeodomain protein Pbx1 (originally identified in pre-B-cell acute lymphoblastic leukemia) binds to the cAMP-regulatory sequence CRS1 of the bovine CYP17 gene and enhances cAMP-dependent transcription; overexpression of Pbx1 in Y1 adrenocortical cells increases CRS1-dependent reporter gene activity. CRS1 affinity purification of nuclear proteins; protein microsequencing; in vitro transcription assay; Pbx1 overexpression in Y1 cells with CRS1-reporter The Journal of biological chemistry Medium 7913464
1993 Dexamethasone inhibits ACTH/cAMP-stimulated CYP17 mRNA accumulation at the transcriptional level via the glucocorticoid receptor (GR), as demonstrated by RU-486 blockade of dexamethasone's inhibitory effect on both endogenous CYP17 mRNA and CYP17-CAT reporter activity in bovine adrenocortical cells. Northern blot analysis; CAT reporter transfection in bovine adrenocortical cells; GR antagonist RU-486; cortisol secretion measurement Molecular endocrinology (Baltimore, Md.) Medium 8385739
1994 Active-site modeling of P450c17 on the crystal structure of P450cam identified residues G111 and G301 as critical for both 17α-hydroxylase and 17,20-lyase activities; G111D and G301I mutations abolished both activities. L102Y and M369L+I371L retained 50–80% activity. No combination of P450c17→P450c21 substitutions conferred 21-hydroxylase activity, indicating substrate specificity requires more than the modeled residues. Homology modeling on P450cam crystal structure; site-directed mutagenesis; COS-1 cell transfection; radiolabeled substrate TLC assay for 17α-hydroxylase, 17,20-lyase, and 21-hydroxylase activities Molecular endocrinology (Baltimore, Md.) Medium 8015556
2004 Deletion of the mouse P450c17 gene causes embryonic lethality by day E7 (prior to gastrulation). Enzyme assays showed a rapid rise in 17-hydroxylase activity between E6 and E7 and C17,20-lyase activity at E7. P450c17 protein localizes to embryonic endoderm at E7. DHEA or 17-OH pregnenolone supplementation failed to rescue knockout embryos, suggesting an unidentified essential function of P450c17 products in early embryogenesis. Gene knockout in 127/SvJ mice (targeted ES cells); immunocytochemistry; enzyme activity assays of wild-type embryos; steroid supplementation rescue experiments Molecular and cellular biology High 15169901
2008 GATA4 activates P450c17 gene expression in early embryonic endoderm cells by binding to the cyp17 promoter region -215/+55. GATA4/6 mRNA increases during F9 stem cell differentiation to visceral/parietal endoderm temporally followed by increased P450c17 mRNA. siRNA knockdown of GATA4 or GATA6 in undifferentiated or differentiated F9 cells diminished endogenous cyp17 expression. Chromatin immunoprecipitation (ChIP) for GATA4 at cyp17 promoter; promoter reporter assays; siRNA knockdown of GATA4/6; qPCR for P450c17 mRNA during retinoic acid/cAMP-induced differentiation Endocrinology Medium 18832096
2017 In glioma, CYP17A1 expression is upregulated by Sp1-mediated DNA demethylation: Sp1 competes with DNMT3a for binding to the CYP17A1 promoter in temozolomide-resistant cells, reducing methylation and increasing CYP17A1 transcription. CYP17A1-mediated DHEA production protects glioma cells from TMZ-induced DNA damage and apoptosis. ChIP assays for Sp1 and DNMT3a at CYP17A1 promoter; bisulfite sequencing; 5-aza-dC demethylation; siRNA knockdown; DHEA supplementation rescue experiments; mouse xenograft models Oncogenesis Medium 28530704
2019 CYP17A1 associates with SAR1a/b on the ER membrane to maintain ER health and redox homeostasis in glioblastoma cells independent of its steroidogenic function. Abiraterone treatment dissociates SAR1a/b from ER-localized CYP17A1, induces SAR1 ubiquitination and degradation, triggers ER stress and ROS accumulation, and causes apoptosis. SAR1 overexpression rescued abiraterone-induced apoptosis. Co-immunoprecipitation of CYP17A1 with SAR1a/b; immunofluorescence localization; abiraterone treatment; SAR1 overexpression rescue; mouse xenograft models (subcutaneous and intracranial) Cancers Medium 31527549
2011 CYP17A1 is expressed in human trophoblasts (syncytiotrophoblasts) and is enzymatically active, producing 17α-hydroxyprogesterone, androstenedione, and their aromatized products de novo. CYP17 mRNA was detected by RT-PCR and protein by Western blot and immunohistochemistry; steroid products increased in the presence of 22-hydroxycholesterol. RT-PCR; Western blot; immunohistochemistry; steroid product measurement by RIA in primary human trophoblasts and JEG-3 cells The Journal of clinical endocrinology and metabolism Medium 21307141
2004 P450c17 and cytochrome b5 colocalize in human androgen-synthesizing tissues (fetal zone of fetal adrenal, zona reticularis of adult adrenal, testicular Leydig cells, theca interna/theca lutein cells of ovary) but not in tissues that lack androgenic function (zona fasciculata, neocortex), providing direct anatomical support for the role of cytochrome b5 in regulating 17,20-lyase activity in vivo. Immunohistochemistry with antibodies specific to P450c17 and cytochrome b5 in human fetal and adult steroidogenic tissues Biology of reproduction Medium 14985252
1995 P450c17 mRNA and protein are expressed in the developing rodent embryonic nervous system (central and peripheral), particularly in neural crest-derived cells and specific brainstem nuclei, establishing that de novo neurosteroid synthesis including DHEA can occur in embryonic neural tissue. RNase protection assay; RT-PCR; immunocytochemistry in mouse and rat embryos from E10.5 to E19.5 Endocrinology Medium 7588260
1996 mRNAs for ACTH (MC-2) receptor, CYP11A1, CYP17, and CYP21A2 are expressed in normal and pathologic human skin, indicating that elements of the steroidogenic pathway are present in skin. RT-PCR of mRNAs in human skin specimens The Journal of clinical endocrinology and metabolism Low 8675607
2020 In triclosan (TCS)-exposed Leydig cells, miR-142-5p targets JAK1/STAT1; STAT1 interacts with and regulates Sp1, which directly binds the DNMT1 promoter; reduced DNMT1 activity increases DAX1 expression, and DAX1 inhibits P450c17, collectively suppressing testosterone production. Bidirectional Co-IP of STAT1 and Sp1; ChIP of Sp1 at DNMT1 promoter; miR-142-5p mimic/inhibitor; siRNA knockdown; qPCR; in vivo rat model The Science of the total environment Medium 32084696

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance? Annals of oncology : official journal of the European Society for Medical Oncology 214 22771826
1996 ACTH receptor, CYP11A1, CYP17 and CYP21A2 genes are expressed in skin. The Journal of clinical endocrinology and metabolism 186 8675607
1999 Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2). Carcinogenesis 169 10469617
1995 Steroidogenic enzyme P450c17 is expressed in the embryonic central nervous system. Endocrinology 165 7588260
1999 P450c17 mutations R347H and R358Q selectively disrupt 17,20-lyase activity by disrupting interactions with P450 oxidoreductase and cytochrome b5. Molecular endocrinology (Baltimore, Md.) 156 9892022
1997 Multiple orphan nuclear receptors converge to regulate rat P450c17 gene transcription: novel mechanisms for orphan nuclear receptor action. Molecular endocrinology (Baltimore, Md.) 138 9178749
2009 Antitumor activity with CYP17 blockade indicates that castration-resistant prostate cancer frequently remains hormone driven. Cancer research 137 19509232
2005 Regulation of 17,20 lyase activity by cytochrome b5 and by serine phosphorylation of P450c17. The Journal of biological chemistry 130 15687493
2013 CYP17 inhibitors--abiraterone, C17,20-lyase inhibitors and multi-targeting agents. Nature reviews. Urology 126 24276076
2002 Protein phosphatase 2A and phosphoprotein SET regulate androgen production by P450c17. The Journal of biological chemistry 112 12444089
2004 GATA-4 and GATA-6 modulate tissue-specific transcription of the human gene for P450c17 by direct interaction with Sp1. Molecular endocrinology (Baltimore, Md.) 111 14988427
2002 Differential inhibition of 17alpha-hydroxylase and 17,20-lyase activities by three novel missense CYP17 mutations identified in patients with P450c17 deficiency. The Journal of clinical endocrinology and metabolism 98 12466376
1999 Prostate cancer associated with CYP17 genotype. Pharmacogenetics 97 10591544
2008 Targeting CYP17: established and novel approaches in prostate cancer. Current opinion in pharmacology 87 18619560
2005 Cytochrome b(5) modulation of 17{alpha} hydroxylase and 17-20 lyase (CYP17) activities in steroidogenesis. The Journal of endocrinology 86 16293774
2014 The diverse chemistry of cytochrome P450 17A1 (P450c17, CYP17A1). The Journal of steroid biochemistry and molecular biology 84 25482340
2006 Sphingosine regulates the transcription of CYP17 by binding to steroidogenic factor-1. Endocrinology 81 16887917
2004 Colocalization of P450c17 and cytochrome b5 in androgen-synthesizing tissues of the human. Biology of reproduction 79 14985252
2003 P450c17 deficiency in Brazilian patients: biochemical diagnosis through progesterone levels confirmed by CYP17 genotyping. The Journal of clinical endocrinology and metabolism 76 14671162
2001 The association between polymorphisms in the CYP17 and 5alpha-reductase (SRD5A2) genes and serum androgen concentrations in men. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 76 11303586
2014 Anticancer activity of a novel selective CYP17A1 inhibitor in preclinical models of castrate-resistant prostate cancer. Molecular cancer therapeutics 74 25351916
2018 Characterization of Sexual Trait Development in cyp17a1-Deficient Zebrafish. Endocrinology 70 30202919
2011 Direct regulation of androgen receptor activity by potent CYP17 inhibitors in prostate cancer cells. The Journal of biological chemistry 68 22174412
2011 The human placenta expresses CYP17 and generates androgens de novo. The Journal of clinical endocrinology and metabolism 67 21307141
2002 A polymorphism in the CYP17 gene and risk of prostate cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 67 11895872
1999 Inhibitors of 17alpha-hydroxylase/17,20-lyase (CYP17): potential agents for the treatment of prostate cancer. Current pharmaceutical design 62 10066888
2000 CYP17 promoter polymorphism and breast cancer in Australian women under age forty years. Journal of the National Cancer Institute 60 11036113
1998 Role of cytochrome P450c17 in polycystic ovary syndrome. Molecular and cellular endocrinology 60 9922107
1994 Modeling and mutagenesis of the active site of human P450c17. Molecular endocrinology (Baltimore, Md.) 60 8015556
2003 HSD17B1 and CYP17 polymorphisms and breast cancer risk among Chinese women in Singapore. International journal of cancer 59 12584742
2002 CAMP-dependent protein kinase enhances CYP17 transcription via MKP-1 activation in H295R human adrenocortical cells. The Journal of biological chemistry 58 12506119
2002 The CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis. Mutagenesis 55 11880540
2013 Active site proton delivery and the lyase activity of human CYP17A1. Biochemical and biophysical research communications 54 24299954
2000 Molecular cloning and characterization of Japanese eel ovarian P450c17 (CYP17) cDNA. General and comparative endocrinology 54 10753574
2007 Cyclic AMP-stimulated interaction between steroidogenic factor 1 and diacylglycerol kinase theta facilitates induction of CYP17. Molecular and cellular biology 51 17664281
1995 Tumor necrosis factor-alpha inhibition of 17 alpha-hydroxylase/C17-20 lyase gene (Cyp17) expression. Endocrinology 50 7628389
1994 A cAMP-regulatory sequence (CRS1) of CYP17 is a cellular target for the homeodomain protein Pbx1. The Journal of biological chemistry 47 7913464
2018 HSD3B1 and Response to a Nonsteroidal CYP17A1 Inhibitor in Castration-Resistant Prostate Cancer. JAMA oncology 46 29049452
2004 Deletion of the mouse P450c17 gene causes early embryonic lethality. Molecular and cellular biology 46 15169901
2001 Pitfalls in characterizing P450c17 mutations associated with isolated 17,20-lyase deficiency. The Journal of clinical endocrinology and metabolism 46 11549685
2013 CYP17A1: a biochemistry, chemistry, and clinical review. Current topics in medicinal chemistry 45 23688130
2008 Genetic aspects of epitestosterone formation and androgen disposition: influence of polymorphisms in CYP17 and UGT2B enzymes. Pharmacogenetics and genomics 45 18496127
2017 Upregulation of CYP17A1 by Sp1-mediated DNA demethylation confers temozolomide resistance through DHEA-mediated protection in glioma. Oncogenesis 44 28530704
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