Affinage

DHCR24

Delta(24)-sterol reductase · UniProt Q15392

Length
516 aa
Mass
60.1 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DHCR24 is an FAD-dependent oxidoreductase anchored in the endoplasmic reticulum membrane that catalyzes the reduction of desmosterol to cholesterol, the final step of the Bloch cholesterol biosynthetic pathway, thereby governing cellular cholesterol levels, lipid raft/caveolae integrity, and membrane-dependent signaling cascades including insulin/Akt, PI3K, and PP2A pathways (PMID:16513830, PMID:16407971, PMID:33710538). Beyond its enzymatic role, DHCR24 functions as a non-enzymatic anti-apoptotic protein by binding p53 and displacing the E3 ligase Mdm2 to stabilize p53, and by inhibiting caspase-3 activation — two activities that are mechanistically separable from its reductase function (PMID:15577914, PMID:17984220, PMID:11007892). DHCR24 transcription is controlled by SREBP-2, LXR, estrogen receptor-α, STAT3, and SOX9 through defined cis-regulatory elements, while its enzymatic activity is post-translationally tuned by phosphorylation at T110/Y299/Y507 and competitively inhibited by the endogenous oxysterol 24(S),25-epoxycholesterol (PMID:22809995, PMID:18815215, PMID:24363437, PMID:22178193). DHCR24 physically interacts with DHCR7 to form a cholesterol biosynthetic metabolon, and genetic deletion in mice causes perinatal lethality with dermopathy, impaired skin barrier, and disrupted lipid-raft-dependent BACE1 compartmentalization and EAAT2 glutamate transporter function (PMID:25637936, PMID:16410790, PMID:16407971, PMID:26628388).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    The discovery that DHCR24 (then seladin-1) directly inhibits caspase-3 activation in response to amyloid-β and oxidative stress established its first known cellular function as an anti-apoptotic factor, independent of its later-recognized enzymatic identity.

    Evidence Overexpression in H4 neuroglioma cells with caspase-3 activity assays and detection of caspase-dependent cleavage product

    PMID:11007892

    Open questions at the time
    • Mechanism of caspase-3 inhibition not defined at molecular level
    • Whether anti-apoptotic function requires reductase activity was unknown
  2. 2004 High

    Identification of DHCR24 as a p53 stabilizer via direct binding to p53 and displacement of Mdm2 revealed a second, non-enzymatic pro-survival mechanism and explained how its loss permits bypass of Ras-induced senescence.

    Evidence Genetic screen, reciprocal co-immunoprecipitation, interaction-disrupting mutants, and senescence/transformation assays

    PMID:15577914

    Open questions at the time
    • Structural basis of DHCR24–p53 and DHCR24–Mdm2 interactions unknown
    • Whether p53 stabilization and caspase-3 inhibition are independent pathways was unresolved
  3. 2006 High

    Studies in DHCR24 knockout mice revealed that the enzyme's cholesterol product is essential for lipid raft/caveolae organization, with loss leading to BACE1 mislocalization and increased Aβ production, impaired insulin/Akt/Bad signaling via caveolae disruption, and perinatal lethal dermopathy with skin barrier failure.

    Evidence DHCR24−/− mice with DRM fractionation, APP processing assays, insulin signaling phosphorylation, histology, and transepidermal water loss measurement

    PMID:16407971 PMID:16410790 PMID:16513830

    Open questions at the time
    • Whether cholesterol supplementation fully rescues all KO phenotypes was incomplete
    • Relative contribution of desmosterol accumulation versus cholesterol depletion was unclear
  4. 2007 High

    Separation-of-function analysis using reductase-dead mutants demonstrated that DHCR24 exerts two mechanistically distinct pro-survival activities: an acute oxidative stress response requiring enzymatic activity, and a chronic p53-stabilizing function independent of both reductase activity and cholesterol production.

    Evidence Reductase activity mutant in neuroblastoma cells and primary neurons; p53 ubiquitination assay; cholesterol depletion experiments

    PMID:17984220

    Open questions at the time
    • Identity of the FAD-dependent reductase substrate relevant to ROS scavenging not defined
    • Structural basis for why enzymatic mutant retains p53 interaction unknown
  5. 2008 High

    Mapping of DHCR24's ER membrane topology and identification of its transcriptional regulators (LXR, estrogen receptor-α, androgen receptor) established the spatial framework for its enzymatic function and the hormonal/metabolic logic controlling its expression.

    Evidence Fluorescent protease protection topology mapping; LXR ChIP and reporter assays with LXRβ−/− mice; ERα-dependent reporter assays; promoter analysis for androgen responsive elements

    PMID:18499757 PMID:18762779 PMID:18815215 PMID:22010141

    Open questions at the time
    • Full membrane topology model debated (single TM vs. extensive membrane association)
    • Direct ChIP for AR binding to DHCR24 promoter not performed
  6. 2009 High

    Linking DHCR24 loss to GGA3 degradation and BACE1 stabilization via caspase-3 activation provided a detailed mechanistic cascade connecting DHCR24 downregulation to amyloidogenic APP processing.

    Evidence siRNA knockdown in SH-SY5Y cells with caspase-3, GGA3, BACE1 activity, and Aβ ELISA assays

    PMID:19815556

    Open questions at the time
    • Whether this cascade operates in vivo in Alzheimer's disease brain not tested
    • Relative contribution of caspase-dependent vs. lipid-raft-dependent BACE1 regulation unclear
  7. 2011 High

    Discovery that the endogenous oxysterol 24(S),25-epoxycholesterol directly and rapidly inhibits DHCR24 enzymatic activity identified a physiological post-translational feedback mechanism for fine-tuning the desmosterol-to-cholesterol ratio.

    Evidence Cell-based desmosterol/cholesterol ratio assays with genetic and pharmacological manipulation of 24,25EC levels across multiple cell types

    PMID:22178193

    Open questions at the time
    • Binding site for 24,25EC on DHCR24 not mapped
    • In vivo relevance of 24,25EC inhibition in specific tissues not established
  8. 2012 High

    Identification of two cooperative SREBP-2 binding sites and NF-Y elements in the DHCR24 promoter established the canonical sterol-regulatory transcriptional mechanism controlling DHCR24 expression.

    Evidence ChIP, EMSA, and luciferase reporter assays with SREBP-2 overexpression

    PMID:22809995

    Open questions at the time
    • Interplay between SREBP-2, LXR, and hormone receptor inputs on DHCR24 expression not integrated
  9. 2013 High

    Demonstration that phosphorylation at T110, Y299, and Y507 regulates DHCR24 enzymatic activity established a post-translational phosphorylation-based control layer distinct from oxysterol inhibition.

    Evidence Site-directed mutagenesis in a reconstituted siRNA-based activity assay in CHO-7 cells; PKC inhibitor treatment

    PMID:24363437

    Open questions at the time
    • Identity of the kinase(s) phosphorylating each site not determined
    • PKC-dependent regulation operates through an unknown mechanism independent of T110/Y299/Y507
  10. 2015 High

    Discovery that DHCR24 physically and functionally interacts with DHCR7 in a metabolon, and that DHCR24 activity is required for DHCR7 function, revealed coordinated channeling of sterol intermediates in the terminal steps of cholesterol biosynthesis; separately, DHCR24's role in maintaining lipid-raft-associated EAAT2 glutamate transporter function linked its enzymatic product to neuroprotection against ischemic injury.

    Evidence Co-immunoprecipitation and functional activity assays with WT/mutant DHCR24; DHCR24+/− mice and U18666A treatment with MCAO model, raft fractionation, and glutamate uptake assay

    PMID:25637936 PMID:26628388

    Open questions at the time
    • Structural basis of DHCR24–DHCR7 metabolon not resolved
    • Whether other cholesterol biosynthetic enzymes participate in the metabolon unknown
  11. 2017 High

    Identification of STAT3 as a direct transcriptional activator of DHCR24 in response to insulin linked DHCR24 to metabolic signaling in cancer, while functional knockdown showed DHCR24 promotes metastatic potential.

    Evidence ChIP-PCR and luciferase assay for STAT3 binding; siRNA knockdown with invasion/migration assays in endometrial cancer cells

    PMID:28112250

    Open questions at the time
    • Whether STAT3 regulation of DHCR24 is specific to endometrial cancer or general unknown
  12. 2021 Medium

    Multiple studies converged to show that DHCR24 loss disrupts caveolae/lipid rafts, leading to dysregulated PI3K/Akt, PP2A, GSK3β, and Ras/MEK/ERK signaling, ultimately causing tau hyperphosphorylation at multiple AD-relevant epitopes — providing a mechanistic link from cholesterol depletion to tauopathy.

    Evidence siRNA knockdown and overexpression in SH-SY5Y neuroblastoma and C8D1A astrocytes; PP2A activity assay; phospho-tau Western blots; pharmacological PP2A activator rescue

    PMID:33710538 PMID:33967735 PMID:35804281

    Open questions at the time
    • In vivo validation of DHCR24-dependent tau hyperphosphorylation lacking
    • Relative importance of different signaling arms (PI3K/Akt vs PP2A vs Ras/ERK) not resolved
    • Studies from single lab, not independently replicated
  13. 2022 High

    SOX9 was identified as a direct transcriptional activator of DHCR24 by ChIP-seq, with enforced DHCR24 expression rescuing proliferation defects of SOX9 loss in DLBCL, establishing a SOX9–DHCR24–cholesterol axis in lymphomagenesis.

    Evidence ChIP-sequencing; SOX9 knockdown with DHCR24 rescue; xenograft mouse models

    PMID:34624089

    Open questions at the time
    • Whether SOX9-DHCR24 axis operates in other cancer types not tested
  14. 2023 High

    Pharmacological DHCR24 inhibition with SH42 was shown to elevate desmosterol, activate LXRα, and reduce hepatic steatosis and inflammation in a strictly LXRα-dependent manner, demonstrating that DHCR24's substrate desmosterol is itself a bioactive signaling lipid.

    Evidence APOE*3-Leiden.CETP mouse model treated with SH42; LXRα KO abolishes all effects; flow cytometry and histology

    PMID:37357756

    Open questions at the time
    • Long-term safety and off-target effects of DHCR24 inhibition not assessed
    • Whether desmosterol accumulation has detrimental effects in other tissues unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the high-resolution structural basis of DHCR24's catalytic mechanism, the molecular details of its interaction with DHCR7 in the metabolon, in vivo validation of the tau hyperphosphorylation cascade, and whether the enzymatic and non-enzymatic (p53/caspase) functions of DHCR24 are coordinated or independent in disease contexts.
  • No crystal or cryo-EM structure of DHCR24 available
  • In vivo relevance of DHCR24-mediated p53 stabilization in cancer not demonstrated
  • Integration of multiple transcriptional inputs (SREBP-2, LXR, ER, AR, STAT3, SOX9) not modeled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 6 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 6 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-5357801 Programmed Cell Death 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4
Partners
CASP3DHCR7MDM2NR1H3SOX9SREBF2STAT3TP53
Complex memberships
DHCR24–DHCR7 cholesterol metabolon

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 DHCR24 (seladin-1) inhibits caspase-3 activation in response to amyloid-beta peptide toxicity and oxidative stress, protecting cells from apoptotic cell death; endogenous seladin-1 is cleaved to a 40 kDa derivative in a caspase-dependent manner during apoptosis. Functional expression in H4 neuroglioma cells with caspase-3 activity assays; Western blot for cleavage product The Journal of neuroscience High 11007892
2004 Seladin-1/DHCR24 binds the p53 amino terminus and displaces E3 ubiquitin ligase Mdm2 from p53, resulting in p53 accumulation; seladin-1 also associates with Mdm2 independently of p53. Loss of seladin-1 bypasses Ras-induced senescence. Mutants disrupting p53 or Mdm2 association are inactive in directing p53-dependent oxidative stress response. Direct genetic screen; co-immunoprecipitation; mutagenesis with phenotypic readout (senescence bypass, transformation assay) Nature High 15577914
2006 Seladin-1-deficient mouse brains have reduced cholesterol and disorganized cholesterol-rich detergent-resistant membrane domains (DRMs), causing displacement of beta-secretase (BACE) from DRMs into APP-containing membrane fractions, increased beta-cleavage of APP, and elevated Abeta peptide levels. Overexpression of seladin-1 increases cholesterol, recruits DRM components, induces plasmin activation, and reduces BACE processing of APP. DHCR24 knockout mice; detergent-resistant membrane fractionation; APP processing assays; seladin-1 overexpression in cells The EMBO journal High 16407971
2006 DHCR24 knockout mice die shortly after birth with lethal dermopathy; DHCR24-deficient epidermis accumulates desmosterol instead of cholesterol, leading to impaired keratinocyte differentiation (aberrant keratin 6, 14, filaggrin, loricrin, involucrin expression), defective skin barrier, and increased transepidermal water loss. Targeted gene disruption (DHCR24-/- mice); histology; immunostaining; trans-epidermal water loss measurement; Lucifer yellow permeability assay The Journal of investigative dermatology High 16410790
2006 DHCR24 knockout mouse embryonic fibroblasts are susceptible to serum withdrawal-induced apoptosis due to disruption of caveolae (cholesterol-rich membrane microdomains), uncoupling of the insulin receptor from caveolae, and impaired insulin-dependent phosphorylation of IRS-1, Akt, and Bad. DHCR24-/- MEFs; subcellular fractionation; immunocytochemistry; insulin signaling phosphorylation assays; cholesterol supplementation rescue Endocrinology High 16513830
2007 DHCR24/seladin-1 exerts a dual prosurvival role: (1) an acute response to oxidative stress via its reductase/cholesterol-synthesizing activity (mutating the reductase activity abolishes protective effect), and (2) a chronic response via stabilization of p53 independent of DHCR24 enzymatic activity and cholesterol, preventing p53 ubiquitination and degradation. Overexpression and siRNA knockdown in neuroblastoma SH-SY5Y cells and primary neurons; reductase activity mutant; p53 ubiquitination assay; cholesterol depletion Molecular and cellular biology High 17984220
2008 Seladin-1/DHCR24 is a fundamental mediator of estrogen-mediated neuroprotection; silencing seladin-1 abolishes 17beta-estradiol protection against Abeta toxicity and oxidative stress. Half-palindromic estrogen responsive elements upstream of the seladin-1 gene drive estrogen receptor alpha-dependent transcription. siRNA silencing; caspase-3 assay; luciferase reporter with ER-alpha co-transfection; identification of ERE in promoter Endocrinology High 18499757
2008 DHCR24 is localized to the endoplasmic reticulum membrane with an N-terminal luminal/C-terminal cytoplasmic orientation; the N-terminal transmembrane domain is essential for ER membrane targeting; ER membrane targeting is not required for ROS scavenging enzymatic activity; anti-apoptotic function of DHCR24 is associated with its caspase-dependent cleavage. Fluorescent protease protection (FPP) assay; transmembrane domain-deletion mutants; H2DCFDA ROS assay; confocal microscopy in neuroblastoma N2A cells Journal of molecular endocrinology High 22010141
2009 Down-regulation of seladin-1 under apoptotic conditions increases caspase-3 activity, leading to enhanced depletion of the BACE1-sorting protein GGA3, subsequent post-translational stabilization of BACE1, elevated BACE1 activity, and increased amyloidogenic APP processing and Abeta production. siRNA knockdown in SH-SY5Y cells; caspase-3 activity assay; Western blot of GGA3 and BACE1; BACE1 activity assay; Abeta ELISA The Journal of biological chemistry High 19815556
2010 DHCR24 expression is upregulated by HCV infection in human hepatocytes, and DHCR24 is required for HCV replication; siRNA silencing of DHCR24 decreases HCV replication in replicon cell lines and JFH-1-infected cells; pharmacological inhibition of DHCR24 with U18666A suppresses HCV replication in vitro and in humanized liver mice. siRNA knockdown; HCV replicon assay; in vivo chimeric mouse model; U18666A pharmacological inhibition Journal of hepatology High 21184787
2011 The oxysterol 24(S),25-epoxycholesterol (24,25EC) rapidly inhibits DHCR24 enzymatic activity, causing accumulation of desmosterol at the expense of cholesterol, independent of changes in DHCR24 protein levels; this inhibition is specific to certain C-25 oxygenated side-chain oxysterols; overexpression of DHCR24 blunts 24,25EC inhibition; endogenous 24,25EC levels are sufficient to reduce DHCR24 activity. Cell-based desmosterol/cholesterol ratio assays; genetic and pharmacological manipulation of 24,25EC levels; DHCR24 overexpression in multiple cell lines Biochimica et biophysica acta High 22178193
2012 DHCR24 is transcriptionally regulated by sterols predominantly through SREBP-2 binding to two cooperative sterol regulatory elements (SREs) in the DHCR24 promoter, assisted by two nearby NF-Y binding sites. Luciferase reporter assays; EMSA; chromatin immunoprecipitation (ChIP); SREBP-2 overexpression Biochimica et biophysica acta High 22809995
2013 DHCR24 enzymatic activity is regulated post-translationally by phosphorylation: mutation of residues T110, Y299, and Y507 inhibits DHCR24 activity; protein kinase C inhibitors ablate DHCR24 activity through a mechanism not involving known phosphorylation sites. siRNA-based activity assay in CHO-7 cells (knocking down endogenous hamster DHCR24 while expressing human DHCR24 mutants); site-directed mutagenesis; PKC inhibitor treatment Journal of lipid research High 24363437
2014 DHCR24 associates extensively with the ER membrane beyond predicted N-terminal transmembrane domains; biochemical evidence indicates the majority of the enzyme is ER membrane-associated. Biochemical fractionation; protease protection assays; bioinformatics topology predictions vs experimental mapping Bioscience reports Medium 27919032
2014 DHCR24 protects neuronal cells from ER stress-induced apoptosis; overexpression of DHCR24 reduces caspase-12 activity, attenuates PERK, JNK, and p38 activation, decreases Bip and CHOP protein levels, reduces intracellular ROS, elevates cholesterol, and promotes well-organized caveolae formation with improved caveolin-1/IGF1R colocalization. Adenoviral DHCR24 overexpression in N2A cells; tunicamycin-induced ER stress; caspase-12 assay; Western blot of UPR markers; H2DCFDA ROS assay; confocal microscopy PloS one Medium 24489783
2015 DHCR24 and DHCR7 (the two terminal enzymes of cholesterol synthesis) physically interact by co-immunoprecipitation; DHCR24 knockdown abolishes DHCR7 activity, and DHCR24 overexpression enhances DHCR7 activity only when a functional DHCR24 is used, indicating a functional metabolon. Co-immunoprecipitation; siRNA knockdown of DHCR24 with measurement of DHCR7 activity; overexpression of wild-type and inactive DHCR24 mutants Journal of lipid research High 25637936
2015 DHCR24 protects against ischemic brain injury by maintaining lipid raft integrity and ensuring proper association of the glutamate transporter EAAT2 with lipid rafts; genetic deletion or pharmacological inhibition of DHCR24 reduces EAAT2-lipid raft association and decreases glutamate uptake in astrocytes, worsening ischemic injury. Dhcr24+/- mice and U18666A pharmacological inhibition; permanent middle cerebral artery occlusion; infarct volume measurement; Western blot for EAAT2 in raft fractions; [3H]-glutamate uptake assay in cultured astrocytes Stroke High 26628388
2017 Insulin induces DHCR24 expression in endometrial cancer cells via STAT3, which directly binds to DHCR24 promoter elements; DHCR24 silencing inhibits metastatic ability and upregulates progesterone receptor expression, sensitizing cells to progestin. ChIP-PCR; luciferase assay; siRNA knockdown; invasion/migration assays Scientific reports High 28112250
2018 DHCR24 transgenic overexpression in mice protects against dilated cardiomyopathy by activating the PI3K/Akt/HKII pathway, reducing Bax translocation and cytochrome c release, and inhibiting caspase-9 and caspase-3 activation; the anti-apoptotic effect is completely abolished by PI3K inhibition and partially by HKII inhibition. Cardiac-specific Dhcr24 transgenic mice; echocardiography; TUNEL assay; Western blot of PI3K/Akt/HKII pathway components; pharmacological inhibitors in H9c2 cells Animal models and experimental medicine Medium 30891546
2019 miR-124 directly targets DHCR24 in cardiomyocytes; miR-124 overexpression increases cardiomyocyte apoptosis while miR-124 inhibition attenuates it; DHCR24 is identified as the functional target mediating the miR-124-dependent regulation of apoptosis in myocardial infarction. miR-124 overexpression/inhibition; luciferase reporter assay confirming DHCR24 as direct target; cardiomyocyte apoptosis assays; intra-myocardial injection of agomiR/antagomiR in mouse MI model Journal of molecular and cellular cardiology High 31100313
2020 DHCR24 overexpression in BV-2 microglia shifts polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype in Abeta25-35-treated cells via activation of Akt/GSK3beta signaling; Akt inhibitor MK2206 reverses DHCR24-mediated anti-inflammatory effects. Lentiviral DHCR24 overexpression; M1/M2 marker measurement (iNOS, IL-1beta, TNF-alpha, arginase-1, IL-4, TGF-beta); Akt inhibitor co-treatment Life sciences Medium 32950573
2021 DHCR24 knockdown reduces plasma membrane cholesterol and caveolin-1, disrupts lipid rafts/caveolae, inhibits PI3K/Akt signaling, and activates GSK3beta and mTOR, leading to tau hyperphosphorylation at Thr181, Ser199, Thr231, Ser262, and Ser396 and inhibition of autophagy; DHCR24 knock-in reverses these effects. siRNA knockdown and overexpression in SH-SY5Y cells; Western blot for tau phospho-epitopes, Akt, GSK3beta, mTOR, LC3, p62; Filipin staining for cholesterol; electron microscopy for autophagosomes Frontiers in aging neuroscience Medium 33967735
2021 DHCR24 knockdown reduces membrane cholesterol and caveolin-1, disrupts lipid raft/caveolae, inhibits PP2A activity (via increased p-PP2Ac at Y307), activates GSK3beta (via increased p-GSK3beta at Y216), leading to tau hyperphosphorylation at Thr181, Thr231, Ser262, Ser396, and Ser422; PP2A activator D-erythro-Sphingosine rescues tau hyperphosphorylation. siRNA knockdown and overexpression in SH-SY5Y cells; PP2A activity assay; Western blot of PP2A, GSK3beta, and tau phospho-epitopes; Filipin staining; pharmacological PP2A activator rescue Neurochemical research Medium 33710538
2022 SOX9 directly transcriptionally activates DHCR24 (identified by ChIP-sequencing), promoting cholesterol synthesis; enforced DHCR24 expression rescues proliferation phenotypes caused by SOX9 knockdown in DLBCL cells; SOX9-DHCR24-cholesterol axis drives lymphomagenesis. ChIP-sequencing; SOX9 knockdown with DHCR24 rescue overexpression; xenograft mouse models; pharmacological cholesterol synthesis inhibition Blood High 34624089
2022 SRSF3 transcriptionally controls DHCR24 expression in colorectal cancer; SRSF3 silencing suppresses DHCR24 expression, increasing ROS and driving apoptosis via the SRSF3/DHCR24/ROS axis. SRSF3 siRNA knockdown; DHCR24 expression measurement; ROS assay; apoptosis assay; SRSF3 inhibitor SFI003 in vitro and in vivo Cell death discovery Medium 35501301
2022 DHCR24 knockdown in C8D1A astrocytes reduces plasma membrane cholesterol and caveolae-associated protein cavin1, disrupts lipid rafts/caveolae, activates Ras/MEK/ERK signaling, and induces tau hyperphosphorylation at Thr181, Ser199, Thr231, Ser262, and Ser396; DHCR24 overexpression prevents this cascade. siRNA knockdown and overexpression in C8D1A astrocytes; Filipin staining; Western blot for cavin1, Ras/MEK/ERK pathway, tau phospho-epitopes; cholesterol measurement Molecular neurobiology Medium 35804281
2023 miR-7 post-transcriptionally represses DHCR24 (and SC5D) expression, blocking late steps of cholesterol biosynthesis; intracranial AAV-mediated miR-7 infusion reduces DHCR24 expression in mouse brain in vivo; cholesterol regulates endogenous miR-7 levels through SREBP2-dependent transcription of the hnRNPK/miR-7 host gene, forming a feedback loop. Luciferase reporter assay (miR-7 targeting DHCR24); AAV intracranial injection; cholesterol biosynthesis assays; SREBP2 ChIP; mouse models of cholesterol accumulation Biochimica et biophysica acta. Gene regulatory mechanisms High 37086967
2023 Pharmacological inhibition of DHCR24 with SH42 increases desmosterol levels in liver and plasma, activates LXRalpha, reduces hepatic lipid content, steatosis, and inflammation (decreasing Kupffer cell activation and monocyte infiltration); LXRalpha deficiency completely abolishes all beneficial effects, establishing a strictly LXRalpha-dependent mechanism. APOE*3-Leiden.CETP mouse model; SH42 DHCR24 inhibitor treatment; LXRalpha KO mice; flow cytometry for liver inflammation; histology; plasma lipid measurements EMBO molecular medicine High 37357756
2008 Androgen receptor directly regulates DHCR24/seladin-1 expression through androgen responsive elements in its promoter; androgen receptor-negative metastatic prostate cancer cells have reduced seladin-1/DHCR24 expression and reduced cholesterol. Promoter analysis identifying androgen responsive elements; androgen ablation treatment in patients with tissue mRNA quantification; comparison of AR-positive vs AR-negative cell lines Laboratory investigation Medium 18762779
2008 DHCR24 (seladin-1) is a direct target gene of liver X receptor (LXR); an LXR response element in the second intron of the DHCR24 gene confers LXR-specific ligand responsiveness in reporter assays; DHCR24 gene expression is significantly decreased in skin of LXRbeta-null mice. Genome-wide LXRalpha ChIP screen; luciferase reporter assay with LXR response element; LXRbeta knockout mouse skin analysis Molecular pharmacology High 18815215
2024 TREM2 upregulation in microglia after traumatic brain injury inhibits DHCR24 expression and upregulates LXR pathway members; LXR inhibition partially reverses the electrophysiological recovery benefits of TREM2 upregulation, establishing DHCR24 as a downstream effector of TREM2 in microglial sterol metabolism regulating white matter repair. TREM2 KO mice; controlled cortical injury model; transcriptomic sequencing of sorted microglia; Western blot; LXR inhibitor (GSK2033); electrophysiological recordings Clinical and translational medicine Medium 38649789

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Intratumoral and peritumoral radiomics for the pretreatment prediction of pathological complete response to neoadjuvant chemotherapy based on breast DCE-MRI. Breast cancer research : BCR 506 28521821
2000 The human DIMINUTO/DWARF1 homolog seladin-1 confers resistance to Alzheimer's disease-associated neurodegeneration and oxidative stress. The Journal of neuroscience : the official journal of the Society for Neuroscience 239 11007892
2004 Regulation of cellular response to oncogenic and oxidative stress by Seladin-1. Nature 165 15577914
2018 A machine learning approach to radiogenomics of breast cancer: a study of 922 subjects and 529 DCE-MRI features. British journal of cancer 164 30033447
2006 The role of seladin-1/DHCR24 in cholesterol biosynthesis, APP processing and Abeta generation in vivo. The EMBO journal 150 16407971
2013 Desmosterol and DHCR24: unexpected new directions for a terminal step in cholesterol synthesis. Progress in lipid research 131 24095826
2007 Dynamic contrast-enhanced ultrasonography (DCE-US) with quantification of tumor perfusion: a new diagnostic tool to evaluate the early effects of antiangiogenic treatment. European radiology 110 18376462
2021 Intratumoral and Peritumoral Radiomics Based on Functional Parametric Maps from Breast DCE-MRI for Prediction of HER-2 and Ki-67 Status. Journal of magnetic resonance imaging : JMRI 109 33955619
2020 Prediction of breast cancer molecular subtypes on DCE-MRI using convolutional neural network with transfer learning between two centers. European radiology 84 33001309
2010 Dynamic contrast-enhanced ultrasonography (DCE-US): a new tool for the early evaluation of antiangiogenic treatment. Targeted oncology 80 20379790
2018 Breast cancer Ki67 expression prediction by DCE-MRI radiomics features. Clinical radiology 77 29970244
2002 Seladin-1 transcription is linked to neuronal degeneration in Alzheimer's disease. Neuroscience 77 12127087
2007 Prosurvival effect of DHCR24/Seladin-1 in acute and chronic responses to oxidative stress. Molecular and cellular biology 76 17984220
2015 The terminal enzymes of cholesterol synthesis, DHCR24 and DHCR7, interact physically and functionally. Journal of lipid research 74 25637936
2011 Dynamic contrast-enhanced ultrasonography (DCE-US) and anti-angiogenic treatments. Discovery medicine 69 21276407
2010 Identification and transcriptional analysis of trans-DCE-producing reductive dehalogenases in Dehalococcoides species. The ISME journal 64 20357835
2006 DHCR24 gene knockout mice demonstrate lethal dermopathy with differentiation and maturation defects in the epidermis. The Journal of investigative dermatology 63 16410790
2011 Evaluation of KRAS mutations, angiogenic biomarkers, and DCE-MRI in patients with advanced non-small-cell lung cancer receiving sorafenib. Clinical cancer research : an official journal of the American Association for Cancer Research 61 21224376
2013 Signaling regulates activity of DHCR24, the final enzyme in cholesterol synthesis. Journal of lipid research 60 24363437
2008 Neuroprotective effects of the Alzheimer's disease-related gene seladin-1. Journal of molecular endocrinology 60 18768664
2008 Seladin-1 is a fundamental mediator of the neuroprotective effects of estrogen in human neuroblast long-term cell cultures. Endocrinology 59 18499757
2009 Down-regulation of seladin-1 increases BACE1 levels and activity through enhanced GGA3 depletion during apoptosis. The Journal of biological chemistry 58 19815556
2010 Augmentation of DHCR24 expression by hepatitis C virus infection facilitates viral replication in hepatocytes. Journal of hepatology 56 21184787
2013 Parameterizing the Logistic Model of Tumor Growth by DW-MRI and DCE-MRI Data to Predict Treatment Response and Changes in Breast Cancer Cellularity during Neoadjuvant Chemotherapy. Translational oncology 55 23730404
2008 Seladin-1/DHCR24 protects neuroblastoma cells against Abeta toxicity by increasing membrane cholesterol content. Journal of cellular and molecular medicine 54 18194465
2020 Evaluating the Relationship Between Dynamic Contrast-Enhanced MRI (DCE-MRI) Parameters and Pathological Characteristics in Breast Cancer. Journal of magnetic resonance imaging : JMRI 52 32524658
2005 Expression of the antiapoptotic gene seladin-1 and octreotide-induced apoptosis in growth hormone-secreting and nonfunctioning pituitary adenomas. The Journal of clinical endocrinology and metabolism 51 16091489
2019 MicroRNA-124 regulates cardiomyocyte apoptosis and myocardial infarction through targeting Dhcr24. Journal of molecular and cellular cardiology 50 31100313
2012 Correlation of a priori DCE-MRI and (1)H-MRS data with molecular markers in neck nodal metastases: Initial analysis. Oral oncology 50 22366441
2009 Assessment of vascular remodeling under antiangiogenic therapy using DCE-MRI and vessel size imaging. Journal of magnetic resonance imaging : JMRI 50 19388117
2006 Relationship between DCE-MRI morphological and functional features and histopathological characteristics of breast cancer. European radiology 50 17149623
2019 Differential diagnosis of nasopharyngeal carcinoma and nasopharyngeal lymphoma based on DCE-MRI and RESOLVE-DWI. European radiology 49 31372786
2022 DCE-MRI Radiomics Analysis in Differentiating Luminal A and Luminal B Breast Cancer Molecular Subtypes. Academic radiology 47 35595629
2020 Genkwadaphnin inhibits growth and invasion in hepatocellular carcinoma by blocking DHCR24-mediated cholesterol biosynthesis and lipid rafts formation. British journal of cancer 47 32958824
2017 Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma. Scientific reports 47 28112250
2006 DHCR24-knockout embryonic fibroblasts are susceptible to serum withdrawal-induced apoptosis because of dysfunction of caveolae and insulin-Akt-Bad signaling. Endocrinology 47 16513830
2011 The endogenous regulator 24(S),25-epoxycholesterol inhibits cholesterol synthesis at DHCR24 (Seladin-1). Biochimica et biophysica acta 46 22178193
2019 Gastric cancer and image-derived quantitative parameters: Part 2-a critical review of DCE-MRI and 18F-FDG PET/CT findings. European radiology 44 31392480
2022 The role of DHCR24 in the pathogenesis of AD: re-cognition of the relationship between cholesterol and AD pathogenesis. Acta neuropathologica communications 43 35296367
2008 Androgen receptor regulation of the seladin-1/DHCR24 gene: altered expression in prostate cancer. Laboratory investigation; a journal of technical methods and pathology 43 18762779
2008 The selective Alzheimer's disease indicator-1 gene (Seladin-1/DHCR24) is a liver X receptor target gene. Molecular pharmacology 41 18815215
2018 Correlation between DCE-MRI radiomics features and Ki-67 expression in invasive breast cancer. Oncology letters 40 30250576
2008 Thyroid hormones promote cell differentiation and up-regulate the expression of the seladin-1 gene in in vitro models of human neuronal precursors. The Journal of endocrinology 39 18434374
1998 Microbial mineralization of VC and DCE under different terminal electron accepting conditions. Anaerobe 39 16887626
2013 DCE-MRI of the hypoxic fraction, radioresponsiveness, and metastatic propensity of cervical carcinoma xenografts. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 38 24231244
2022 Oncogenic role of the SOX9-DHCR24-cholesterol biosynthesis axis in IGH-BCL2+ diffuse large B-cell lymphomas. Blood 36 34624089
2011 Functional and structural characteristics of tumor angiogenesis in lung cancers overexpressing different VEGF isoforms assessed by DCE- and SSCE-MRI. PloS one 36 21283766
2012 Cell membrane water exchange effects in prostate DCE-MRI. Journal of magnetic resonance (San Diego, Calif. : 1997) 34 22578558
2008 Intermittent high glucose concentrations reduce neuronal precursor survival by altering the IGF system: the involvement of the neuroprotective factor DHCR24 (Seladin-1). The Journal of endocrinology 34 18612048
2014 3 β-hydroxysteroid-Δ 24 reductase (DHCR24) protects neuronal cells from apoptotic cell death induced by endoplasmic reticulum (ER) stress. PloS one 33 24489783
2012 Sterols regulate 3β-hydroxysterol Δ24-reductase (DHCR24) via dual sterol regulatory elements: cooperative induction of key enzymes in lipid synthesis by Sterol Regulatory Element Binding Proteins. Biochimica et biophysica acta 33 22809995
2015 Correlation of tumor characteristics derived from DCE-MRI and DW-MRI with histology in murine models of breast cancer. NMR in biomedicine 31 26332194
2022 Intra- and Peritumoral Radiomics Model Based on Early DCE-MRI for Preoperative Prediction of Molecular Subtypes in Invasive Ductal Breast Carcinoma: A Multitask Machine Learning Study. Frontiers in oncology 30 35814460
2019 Neuroinflammatory Reactions in the Brain of 1,2-DCE-Intoxicated Mice during Brain Edema. Cells 30 31461951
2023 Inhibition of DHCR24 activates LXRα to ameliorate hepatic steatosis and inflammation. EMBO molecular medicine 29 37357756
2021 DHCR24 Knock-Down Induced Tau Hyperphosphorylation at Thr181, Ser199, Thr231, Ser262, Ser396 Epitopes and Inhibition of Autophagy by Overactivation of GSK3β/mTOR Signaling. Frontiers in aging neuroscience 29 33967735
2021 DCE-MRI quantitative transport mapping for noninvasively detecting hypoxia inducible factor-1α, epidermal growth factor receptor overexpression, and Ki-67 in nasopharyngeal carcinoma patients. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 29 34592360
2009 New insights on the neuroprotective role of sterols and sex steroids: the seladin-1/DHCR24 paradigm. Frontiers in neuroendocrinology 28 19351544
2023 DHCR24 reverses Alzheimer's disease-related pathology and cognitive impairment via increasing hippocampal cholesterol levels in 5xFAD mice. Acta neuropathologica communications 26 37344916
2021 DCE-MRI in Glioma, Infiltration Zone and Healthy Brain to Assess Angiogenesis: A Biopsy Study. Clinical neuroradiology 26 33900414
2019 Histogram analysis of DCE-MRI for chemoradiotherapy response evaluation in locally advanced esophageal squamous cell carcinoma. La Radiologia medica 26 31605354
2012 The membrane topological analysis of 3β-hydroxysteroid-Delta24 reductase (DHCR24) on endoplasmic reticulum. Journal of molecular endocrinology 26 22010141
2008 Macromolecular dynamic contrast-enhanced (DCE)-MRI detects reduced vascular permeability in a prostate cancer bone metastasis model following anti-platelet-derived growth factor receptor (PDGFR) therapy, indicating a drop in vascular endothelial growth factor receptor (VEGFR) activation. Magnetic resonance in medicine 25 18816866
2022 A novel SRSF3 inhibitor, SFI003, exerts anticancer activity against colorectal cancer by modulating the SRSF3/DHCR24/ROS axis. Cell death discovery 24 35501301
2020 DHCR24 overexpression modulates microglia polarization and inflammatory response via Akt/GSK3β signaling in Aβ25-35 treated BV-2 cells. Life sciences 24 32950573
2024 TREM2 alleviates white matter injury after traumatic brain injury in mice might be mediated by regulation of DHCR24/LXR pathway in microglia. Clinical and translational medicine 23 38649789
2010 Inhibition of DHCR24/seladin-1 impairs cellular homeostasis in prostate cancer. The Prostate 23 20166102
2008 Increased expression of aquaporin-3 in the epidermis of DHCR24 knockout mice. The British journal of dermatology 23 18241265
2012 Is seladin-1 really a selective Alzheimer's disease indicator? Journal of Alzheimer's disease : JAD 22 22387408
2005 Seladin-1/DHCR24 expression in normal ovary, ovarian epithelial and granulosa tumours. Clinical endocrinology 22 15963070
2022 Dehydrocholesterol Reductase 24 (DHCR24): Medicinal Chemistry, Pharmacology and Novel Therapeutic Options. Current medicinal chemistry 21 34781860
2022 DHCR24 Knockdown Induces Tau Hyperphosphorylation at Thr181, Ser199, Ser262, and Ser396 Sites via Activation of the Lipid Raft-Dependent Ras/MEK/ERK Signaling Pathway in C8D1A Astrocytes. Molecular neurobiology 21 35804281
2018 A DCE-MRI Driven 3-D Reaction-Diffusion Model of Solid Tumor Growth. IEEE transactions on medical imaging 20 29533893
2018 Dhcr24 activates the PI3K/Akt/HKII pathway and protects against dilated cardiomyopathy in mice. Animal models and experimental medicine 20 30891546
2015 Seladin-1/DHCR24 Is Neuroprotective by Associating EAAT2 Glutamate Transporter to Lipid Rafts in Experimental Stroke. Stroke 20 26628388
2014 DHCR24 associates strongly with the endoplasmic reticulum beyond predicted membrane domains: implications for the activities of this multi-functional enzyme. Bioscience reports 20 27919032
2017 Data-driven mapping of hypoxia-related tumor heterogeneity using DCE-MRI and OE-MRI. Magnetic resonance in medicine 19 28856728
2007 Seladin-1 expression in rat adrenal gland: effect of adrenocorticotropic hormone treatment. The Journal of endocrinology 19 17210742
2007 The association study between DHCR24 polymorphisms and Alzheimer's disease. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 19 17510943
2021 Dynamic contrast-enhanced MRI of nasopharyngeal carcinoma: correlation of quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters with hypoxia-inducible factor 1α expression and tumor grade/stage. Annals of palliative medicine 18 33725777
2017 A comparison of Bayesian and non-linear regression methods for robust estimation of pharmacokinetics in DCE-MRI and how it affects cancer diagnosis. Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society 18 28192761
2012 Promoter analysis of the DHCR24 (3β-hydroxysterol Δ(24)-reductase) gene: characterization of SREBP (sterol-regulatory-element-binding protein)-mediated activation. Bioscience reports 18 23050906
2019 Detection of Local Recurrence in Patients with Head and Neck Squamous Cell Carcinoma Using Voxel-Based Color Maps of Initial and Final Area under the Curve Values Derived from DCE-MRI. AJNR. American journal of neuroradiology 17 31320461
2022 Predicting hormone receptors and PAM50 subtypes of breast cancer from multi-scale lesion images of DCE-MRI with transfer learning technique. Computers in biology and medicine 16 36201887
2014 DCE-MRI assessment of the effect of Epstein-Barr virus-encoded latent membrane protein-1 targeted DNAzyme on tumor vasculature in patients with nasopharyngeal carcinomas. BMC cancer 16 25407966
2024 Enhancing pathological complete response prediction in breast cancer: the role of dynamic characterization of DCE-MRI and its association with tumor heterogeneity. Breast cancer research : BCR 15 38745321
2020 A variant near DHCR24 associates with microstructural properties of white matter and peripheral lipid metabolism in adolescents. Molecular psychiatry 15 31900429
2016 Demonstration of DCE-MRI as an early pharmacodynamic biomarker of response to VEGF Trap in glioblastoma. Journal of neuro-oncology 15 27576699
2023 "MiR-7 controls cholesterol biosynthesis through posttranscriptional regulation of DHCR24 expression". Biochimica et biophysica acta. Gene regulatory mechanisms 14 37086967
2016 Characterization of cervical lymph nodes using DCE-MRI: Differentiation between metastases from SCC of head and neck and benign lymph nodes. Clinical hemorheology and microcirculation 14 27258201
2014 DHCR24 is an independent predictor of progression in patients with non-muscle-invasive urothelial carcinoma, and its functional role is involved in the aggressive properties of urothelial carcinoma cells. Annals of surgical oncology 14 24562935
2012 Testosterone up-regulates seladin-1 expression by iAR and PI3-K/Akt signaling pathway in C6 cells. Neuroscience letters 14 22405892
2009 Seladin-1 and testicular germ cell tumours: new insights into cisplatin responsiveness. The Journal of pathology 14 19844922
2024 DHCR24 in Tumor Diagnosis and Treatment: A Comprehensive Review. Technology in cancer research & treatment 13 38847653
2021 DHCR24 Knockdown Lead to Hyperphosphorylation of Tau at Thr181, Thr231, Ser262, Ser396, and Ser422 Sites by Membrane Lipid-Raft Dependent PP2A Signaling in SH-SY5Y Cells. Neurochemical research 13 33710538
2020 18F-FDG PET and DCE kinetic modeling and their correlations in primary NSCLC: first voxel-wise correlative analysis of human simultaneous [18F]FDG PET-MRI data. EJNMMI research 13 32734484
2019 Inhibition of DHCR24 increases the cisplatin-induced damage to cochlear hair cells in vitro. Neuroscience letters 13 31091460
2018 Apolipoprotein M induces inhibition of inflammatory responses via the S1PR1 and DHCR24 pathways. Molecular medicine reports 13 30569161
2012 Simvastatin modulates the Alzheimer's disease-related gene seladin-1. Journal of Alzheimer's disease : JAD 13 21987590
2009 [Seladin-1/DHCR24: a key protein of cell homeostasis and cholesterol biosynthesis]. Postepy higieny i medycyny doswiadczalnej (Online) 13 19597241