Affinage

CBR1

Carbonyl reductase [NADPH] 1 · UniProt P16152

Round 2 corrected
Length
277 aa
Mass
30.4 kDa
Annotated
2026-04-28
108 papers in source corpus 25 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CBR1 is an NADPH-dependent monomeric short-chain dehydrogenase/reductase that catalyzes the reduction of a broad range of carbonyl substrates—including prostaglandins (PGE2→PGF2α), anthracycline anticancer drugs (daunorubicin→daunorubicinol, doxorubicin→doxorubicinol), quinones, and xenobiotic ketones—thereby governing drug metabolism, prostaglandin signaling, and intracellular redox homeostasis (PMID:7005231, PMID:17344335, PMID:24654784). Transcription of CBR1 is induced by AHR via xenobiotic response elements, Nrf2 via antioxidant response elements, and glucocorticoid receptor binding at the CBR1 promoter, while its mRNA is post-transcriptionally stabilized by the m6A reader IGF2BP2 and post-translationally repressed by miR-1290 downstream of E2F2 (PMID:17569794, PMID:23247010, PMID:24654784, PMID:40526983, PMID:41310140). By controlling ROS levels and prostaglandin metabolism, CBR1 suppresses NF-κB/MAPK-dependent inflammation, protects against ferroptosis, confers anthracycline resistance in cancer cells through a SETD4-dependent stemness/quiescence program, and regulates blood pressure; triplication of CBR1 in Down syndrome mouse models reduces PGE2 and contributes to spatial memory impairment and hypotension, effects alleviated by genetic normalization of Cbr1 copy number (PMID:25818598, PMID:34673014, PMID:41490728, PMID:32843708). The V88I polymorphism alters catalytic efficiency, NADPH affinity, and flavonoid inhibitor sensitivity, establishing it as a pharmacogenetic determinant of anthracycline cardiotoxicity risk (PMID:17344335, PMID:22124095).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1981 High

    Purification of CBR1 from human brain established it as an NADPH-dependent monomeric reductase with broad substrate specificity encompassing quinones, prostaglandins, daunorubicin, and ketones, unifying previously separate enzymatic activities under a single protein.

    Evidence Protein purification to homogeneity from human brain with substrate profiling, stereochemical hydride-transfer analysis, and inhibitor studies

    PMID:7005231

    Open questions at the time
    • No crystal structure at this stage
    • Tissue distribution beyond brain not characterized
    • Endogenous physiological substrate hierarchy unknown
  2. 1993 High

    Mapping CBR1 to chromosome 21q22.12 and demonstrating gene-dosage-dependent elevation of mRNA and activity in trisomy 21 cells raised the possibility that CBR1 overexpression contributes to Down syndrome phenotypes.

    Evidence FISH mapping with enzyme activity and mRNA quantification in aneuploid lymphoblast lines

    PMID:8432528

    Open questions at the time
    • Specific DS phenotypes attributable to CBR1 dosage not yet identified
    • Gene dosage effect in tissues beyond lymphoblasts not assessed
  3. 2007 High

    Identification of the V88I functional polymorphism revealed that a single residue change alters Vmax, NADPH affinity, and inhibitor sensitivity, providing the first molecular explanation for inter-individual variation in CBR1-dependent drug metabolism.

    Evidence Recombinant enzyme kinetics and isothermal titration calorimetry for NADPH binding with both isoforms

    PMID:17344335

    Open questions at the time
    • Population frequency and clinical penetrance of V88I not yet established
    • Structural basis for altered cofactor affinity not resolved
  4. 2007 High

    Discovery that AHR induces CBR1 transcription through two XRE elements, validated in Ahr-knockout mice, established the first transcriptional regulatory axis for CBR1 and linked xenobiotic sensing to carbonyl reductase capacity.

    Evidence Promoter-reporter deletion/mutation analysis, TCDD/β-naphthoflavone induction, and Ahr−/− mouse model

    PMID:17569794 PMID:22531821

    Open questions at the time
    • Whether AHR-CBR1 induction is protective or detrimental in chronic xenobiotic exposure not resolved
    • Contribution of distal vs. proximal XRE in vivo unknown
  5. 2008 High

    Structure–function analysis of the CBR1 substrate-binding loop (residues 236–244) identified the molecular determinants that confer its dramatically higher catalytic efficiency compared to CBR3, explaining paralog specificity.

    Evidence Site-directed mutagenesis with chimeric CBR1/CBR3 constructs and enzyme kinetics for isatin and phenanthrenequinone

    PMID:19061875

    Open questions at the time
    • Full structural model of the substrate-binding pocket with bound substrate not available
    • Whether these residues similarly govern anthracycline specificity not tested
  6. 2011 Medium

    A pharmacogenetic study in childhood cancer survivors linked CBR3 V244M genotype—and to a lesser extent CBR1 1096G>A—to anthracycline cardiomyopathy risk, translating earlier enzymology into a clinically relevant pharmacogenomic marker.

    Evidence Case-control study in 487 childhood cancer survivors with conditional logistic regression

    PMID:22124095

    Open questions at the time
    • CBR1 genotype effect did not reach independent significance in this cohort
    • Replication in prospective studies needed
    • Mechanistic link between CBR1 genotype and cardiotoxic metabolite levels in patients not directly measured
  7. 2012 High

    Nrf2 was established as a second transcriptional activator of CBR1, binding an ARE in the promoter, thereby connecting oxidative stress sensing to CBR1 induction and positioning CBR1 within the cellular antioxidant defense program.

    Evidence EMSA, luciferase reporter with ARE mutation, Nrf2 cotransfection, and BHA treatment in HepG2 cells

    PMID:23247010

    Open questions at the time
    • Relative contribution of Nrf2 vs. AHR to basal CBR1 expression not quantified
    • Nrf2-CBR1 axis not validated in vivo at this stage
  8. 2012 Medium

    Cbr1 haploinsufficiency in a mouse tumor model demonstrated that CBR1 enzymatic conversion of doxorubicin limits its therapeutic efficacy in vivo, with unexpected sex-dependent expression differences explaining differential tumor responses.

    Evidence Cbr1+/− mice crossed with PyVT mammary tumor model; sex-specific Western blotting of Cbr1 in liver/kidney

    PMID:22343424

    Open questions at the time
    • Molecular basis of sex-specific Cbr1 expression not elucidated
    • Cardiotoxicity was not measured alongside efficacy
  9. 2014 High

    ChIP-validated glucocorticoid receptor binding at the CBR1 promoter, combined with functional knockdown and inhibitor experiments, identified GR as a third transcriptional regulator and established that cortisol-driven PGE2→PGF2α conversion in amnion is mediated by CBR1.

    Evidence ChIP for GR and RNA Pol II, siRNA knockdown of GR and CBR1, RU486 antagonism, PGF2α ELISA in primary human amnion fibroblasts

    PMID:24654784

    Open questions at the time
    • Role of CBR1-mediated prostaglandin conversion in parturition timing not tested
    • Whether GR directly or indirectly occupies the CBR1 promoter (cofactor requirements) not resolved
  10. 2015 Medium

    Delivery of Tat-CBR1 into macrophages demonstrated that CBR1 enzymatic activity suppresses NF-κB and MAPK signaling, establishing CBR1 as an active anti-inflammatory effector rather than merely a passive metabolic enzyme.

    Evidence Tat-CBR1 protein transduction into RAW 264.7 macrophages with LPS stimulation; TPA ear edema model in mice

    PMID:25818598

    Open questions at the time
    • Whether the anti-inflammatory effect requires catalytic activity or is mediated by protein–protein interaction not distinguished
    • Endogenous substrate responsible for NF-κB suppression not identified
  11. 2016 Medium

    Identification of RACK1 as a physical interactor that stabilizes CBR1 protein connected CBR1 regulation to the RACK1 signaling scaffold and showed that RACK1-CBR1 axis controls ROS and cell survival.

    Evidence Co-immunoprecipitation, RACK1 siRNA, CBR1 overexpression rescue, ROS measurement in HCC cells

    PMID:28105239

    Open questions at the time
    • Reciprocal Co-IP not reported
    • Binding interface and stoichiometry unknown
    • Whether RACK1 stabilizes CBR1 by blocking ubiquitination or other degradation pathways not determined
  12. 2020 High

    Genetic normalization of Cbr1 copy number in a Down syndrome mouse model demonstrated that CBR1 triplication reduces PGE2 and impairs spatial memory, directly linking CBR1 gene dosage to a specific DS cognitive phenotype through prostaglandin metabolism.

    Evidence Ts1Cje mice with Cbr1 copy-number normalization; hippocampal electrophysiology, behavioral testing, PGE2 measurement

    PMID:32843708

    Open questions at the time
    • Whether PGE2 supplementation alone rescues memory not tested
    • Contribution of CBR1 to other DS phenotypes (cardiac, immune) not assessed
  13. 2021 High

    CBR1 inhibition by chrysin was shown to trigger ROS-dependent autophagic degradation of ferritin heavy chain, elevating free iron and inducing ferroptosis in pancreatic cancer cells, revealing a previously unknown role for CBR1 in ferroptosis suppression.

    Evidence Direct binding assay, enzymatic inhibition, ROS/ferroptosis markers, siRNA knockdown, and xenograft validation

    PMID:34673014

    Open questions at the time
    • Specific CBR1 substrate whose reduction prevents ROS accumulation not identified
    • Whether ferroptosis induction generalizes to other cancer types not established
  14. 2024 Medium

    CBR1 overexpression was found to promote cancer stemness and quiescence via SETD4, and CBR1 inhibition disrupted this program to sensitize NSCLC cells to cisplatin, positioning CBR1 as a druggable node linking metabolic activity to stem-cell-like drug resistance.

    Evidence shRNA/pharmacological CBR1 inhibition, SETD4 rescue, flow cytometry for G0, xenograft model

    PMID:41490728

    Open questions at the time
    • How CBR1 enzymatic activity regulates SETD4 expression is mechanistically undefined
    • Whether this axis operates in non-NSCLC cancers not tested
  15. 2025 Medium

    Post-transcriptional regulation of CBR1 was established via IGF2BP2/m6A-dependent mRNA stabilization and E2F2→miR-1290-mediated suppression, expanding the regulatory landscape of CBR1 beyond transcriptional control.

    Evidence IGF2BP2 knockdown with mRNA stability assay and CBR1 rescue in colitis model; ChIP and dual-luciferase for E2F2/miR-1290/CBR1 axis in PSD rat model

    PMID:40526983 PMID:41310140

    Open questions at the time
    • Whether m6A modification and miR-1290 regulation operate in the same tissues/contexts not known
    • Specific m6A site(s) on CBR1 mRNA not mapped
  16. 2025 Medium

    Nrf2-CBR1 axis was independently validated in osteoblasts as protective against PGE2-induced ferroptosis via vitamin K2-mediated Nrf2 stabilization, confirming the Nrf2-CBR1 regulatory connection in a non-cancer, non-liver context.

    Evidence EMSA, ChIP-qPCR for Nrf2 at CBR1 promoter, Keap1 ubiquitination assay, in vivo osteoporosis model

    PMID:40721947

    Open questions at the time
    • Whether CBR1 directly metabolizes PGE2 to reduce ferroptosis or acts through ROS clearance not distinguished
    • Relative contribution of CBR1 vs. other Nrf2 target genes to ferroptosis protection unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous substrate hierarchy of CBR1 in different tissues remains undefined, and the mechanism by which CBR1 enzymatic activity controls SETD4-dependent stemness signaling and NF-κB/MAPK suppression has not been resolved at the metabolite level.
  • No metabolomics-based identification of the dominant endogenous CBR1 substrate in vivo
  • Structural basis for isoform-specific inhibitor sensitivity (V88 vs I88) not crystallographically resolved
  • Whether CBR1 anti-inflammatory and ferroptosis-protective roles converge on the same substrate or represent distinct activities is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 9 GO:0016209 antioxidant activity 3
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-8953897 Cellular responses to stimuli 6 R-HSA-9748784 Drug ADME 6 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953854 Metabolism of RNA 2
Partners
AHRGRIGF2BP2NRF2RACK1SETD4

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1981 Human carbonyl reductase 1 (CBR1) was purified to homogeneity from human brain as an NADPH-dependent monomeric enzyme (MW ~30,000 Da) that reduces quinones (menadione, ubiquinone), aldehydes, prostaglandins E and A, daunorubicin, and 3-ketosteroids; the pro-4S hydrogen of NADPH is transferred to substrate; flavonoids (quercetin, rutin), indomethacin, and dicoumarol inhibit activity; the enzyme is identical to prostaglandin 9-ketoreductase and xenobiotic ketone reductase. Protein purification to homogeneity, enzyme kinetics, substrate profiling, inhibitor studies, stereochemical analysis of hydride transfer The Journal of biological chemistry High 7005231
1993 The human CBR gene was mapped by high-resolution fluorescence in situ hybridization to chromosome 21q22.12, near SOD1 (21q22.11); trisomy 21 lymphoblasts showed gene dosage effects with increased CBR mRNA and elevated aldo-keto reductase and quinone reductase activities proportional to chromosome 21 ploidy. FISH mapping, mRNA quantification, enzyme activity assays in aneuploid cell lines Genomics High 8432528
2007 A functional SNP in CBR1 (V88I) alters enzyme kinetics and cofactor binding: the CBR1 V88 isoform has higher Vmax for daunorubicin and PGE2 and produces more cardiotoxic daunorubicinol; CBR1 I88 has higher NADPH binding affinity (Kd 3.8 µM vs 6.3 µM for V88) and different sensitivity to flavonoid inhibitor rutin (IC50 15 µM vs 54 µM), establishing V88I as the first functional genetic determinant of CBR1 catalytic activity. Recombinant protein expression, enzyme kinetics, isothermal titration calorimetry (ITC) for cofactor binding, molecular modeling Drug metabolism and disposition High 17344335
2007 Transcription of CBR1 is induced ~5-fold by the aryl hydrocarbon receptor (AHR) ligand beta-naphthoflavone and by TCDD; two xenobiotic response elements (XREs at -122 and -5783 bp) mediate AHR-dependent induction; the -122XRE is required for proximal promoter activity; TCDD induces hepatic Cbr1 mRNA and protein in Ahr+/- but not Ahr-/- mice, establishing AHR as a transcriptional regulator of CBR1. Luciferase reporter assays, AHR ligand treatment, Ahr knockout mouse model, mRNA/protein quantification, deletion/mutation analysis of promoter constructs Molecular pharmacology High 17569794
2008 The cardioprotectant flavonoid monoHER inhibits CBR1 activity competitively for daunorubicin (Ki=45 µM) and uncompetitively for menadione (Ki=33 µM); CBR1 I88 genotype shows lower IC50 values for monoHER, triHER, and quercetin compared to V88, demonstrating that the V88I polymorphism dictates differential inhibition by flavonoids. Enzyme kinetic inhibition studies with recombinant CBR1 V88 and I88 isoforms, IC50 and Ki determination Pharmaceutical research High 18449627
2008 Site-directed mutagenesis of the substrate-binding site of CBR1 and CBR3 revealed that nine residues (236–244) near the catalytic center plus P230 of CBR3 are responsible for the dramatic difference in catalytic efficiency toward isatin (CBR1 kcat/Km=13.5 µM⁻¹min⁻¹ vs CBR3 0.018 µM⁻¹min⁻¹); mutating these residues to CBR1 equivalents increased CBR3 efficiency to 5.7 µM⁻¹min⁻¹. Site-directed mutagenesis, recombinant protein expression in E. coli, enzyme kinetics with isatin and 9,10-phenanthrenequinone, molecular docking Chemico-biological interactions High 19061875
2011 CBR1 (1096G>A) and CBR3 (V244M) polymorphisms modulate anthracycline-related cardiomyopathy risk in childhood cancer survivors: carriers of the CBR3 V244M G/G genotype have significantly increased cardiomyopathy risk at low-to-moderate anthracycline doses (OR 5.48), whereas variant allele carriers show no increased risk at these doses, consistent with CBR3 GG allele producing higher levels of cardiotoxic alcohol metabolites. Clinical pharmacogenetics study in 487 childhood cancer survivors, conditional logistic regression Journal of clinical oncology Medium 22124095
2012 The transcription factor Nrf2 binds an antioxidant response element (ARE) in the CBR1 promoter region (-2062 bp to TSS) and induces CBR1 mRNA and protein expression; BHA (a Nrf2 activator) induces CBR1 in HepG2 cells; ARE mutation abolishes Nrf2-mediated induction; Chinese hamster Cbr1 homologs also contain functional AREs; Nrf2 is thus established as a transcriptional regulator of CBR1. Luciferase reporter assay, EMSA, site-directed mutagenesis of ARE, Nrf2 cotransfection, BHA treatment in HepG2 cells Chemico-biological interactions High 23247010
2012 Cbr1 heterozygous null mice show sex-dependent differences in doxorubicin efficacy against mammary tumors; Cbr1+/- male mice show improved tumor regression compared to wild-type, correlating with markedly higher Cbr1 protein expression in female kidney and liver (explaining why female Cbr1+/- mice do not show similar enhancement), demonstrating that CBR1 enzymatic conversion of doxorubicin reduces therapeutic efficacy. Cbr1+/- mouse genetic model crossed with PyVT mammary tumor model, Western blotting for sex-specific Cbr1 expression, tumor regression measurement Anti-cancer drugs Medium 22343424
2012 Benzo[a]pyrene (B[a]P), a cigarette smoke constituent and AHR ligand, upregulates CBR1 mRNA (~3-fold) and protein (~1.5-fold) in A549 lung cancer cells; enhanced AhR nuclear translocation occurs upon B[a]P exposure; the proximal -122XRE motif mediates reporter induction by B[a]P and shows increased binding of AhR/Arnt complexes in nuclear extracts from treated cells. RT-PCR, Western blot, promoter reporter assay with XRE deletion/mutation, EMSA with nuclear extracts, AhR nuclear translocation imaging Toxicology letters High 22531821
2014 Cortisol induces CBR1 expression in human amnion fibroblasts via glucocorticoid receptor (GR): siRNA knockdown of GR or GR antagonist RU486 attenuates cortisol-induced CBR1 upregulation; ChIP shows increased GR and RNA Pol II enrichment at the CBR1 promoter; CBR1 knockdown or rutin-mediated inhibition reduces both basal and cortisol-stimulated PGF2α production, demonstrating CBR1 converts PGE2 to PGF2α downstream of cortisol/GR signaling in amnion. siRNA knockdown of GR and CBR1, GR antagonist treatment, ChIP, PGF2α ELISA, CBR1 inhibitor (rutin) studies in primary human amnion fibroblasts Endocrinology High 24654784
2015 Tat-CBR1 fusion protein transduced into macrophages suppresses LPS-induced COX-2, nitric oxide, and PGE2 expression, and inhibits NF-κB and MAPK (p38, ERK, JNK) activation; topical Tat-CBR1 also reduces TPA-induced skin inflammation in mice, establishing CBR1 as an anti-inflammatory regulator acting through suppression of NF-κB and MAPK pathways. Cell-penetrating Tat-CBR1 protein transduction into RAW 264.7 macrophages, LPS stimulation, Western blot for NF-κB/MAPK pathway components, TPA mouse ear edema model Toxicology and applied pharmacology Medium 25818598
2015 Canine carbonyl reductase 1 (cbr1) metabolizes daunorubicin to daunorubicinol and menadione; two isoforms (D218 and V218) show different kinetic parameters (Km and Vmax); rutin competitively inhibits both isoforms (Ki ~1.4–1.84 µM), establishing canine cbr1 as an anthracycline reductase ortholog of human CBR1. Recombinant protein expression in E. coli, enzyme kinetics with daunorubicin and menadione, competitive inhibition studies with rutin Drug metabolism and disposition High 25918240
2016 RACK1 physically interacts with CBR1 and sustains its protein stability; RACK1 knockdown increases intracellular ROS following TNF-α or H2O2 stimulation in HCC cells; overexpression of CBR1 reverses the enhanced cell death caused by RACK1 knockdown, establishing RACK1 as a protein stability regulator of CBR1 in the ROS/cell survival pathway. Co-immunoprecipitation, RACK1 siRNA knockdown, CBR1 overexpression rescue, ROS measurement, cell viability assay Oncology letters Medium 28105239
2016 Yeast Cbr1 (cytochrome b5 reductase) is an NADH-dependent reductase for Dph3, the electron donor required for both diphthamide biosynthesis and tRNA wobble uridine modification; identified by proteomics and validated by direct biochemical assay, establishing a regulatory link between cellular metabolic redox state (NADH) and protein/tRNA modification pathways. Proteomic identification of Cbr1 as Dph3 reductase, in vitro NADH-dependent Dph3 reduction assay Nature chemical biology High 27694803
2016 Canine cbr1 transcription is dependent on Sp1 binding to the proximal promoter; ChIP confirms Sp1 enrichment at the cbr1 promoter; Sp1-DNA binding inhibition reduces cbr1 mRNA by 54% and carbonyl reductase activity; Sp1 transactivation increases cbr1 mRNA by 67%; variable Sp1 motif copy number in canine cbr1 5'-UTR impacts transcription, identifying Sp1 as a key transcriptional regulator. Luciferase reporter assays, site-directed mutagenesis of Sp1 sites, ChIP, Sp1 inhibitor treatment, Sp1 transactivation overexpression, enzyme activity measurement Gene High 27506315
2018 CBR1 rs9024 (1096G>A) genotype status impacts the bioactivation of loxoprofen in human liver: livers homozygous for the G allele show 33% higher trans-OH loxoprofen/cis-OH loxoprofen synthesis ratios compared to GA heterozygotes, establishing CBR1 as the enzyme responsible for stereoselective reduction of loxoprofen to its bioactive trans-OH metabolite. Human liver cytosol incubations with loxoprofen, metabolite quantification by mass spectrometry, genotype-phenotype correlation in lymphoblastoid cell lines Biopharmaceutics & drug disposition Medium 29851133
2020 Cbr1 triplication in Down syndrome model mice (Ts1Cje) reduces prostaglandin E2 (PGE2) levels and contributes to spatial memory impairment; restoring Cbr1 to two copies (Ts1Cje;Cbr1+/+/-) alleviates PGE2 reduction and memory deficits but does not reverse GABAB receptor-mediated over-inhibition; demonstrating Cbr1 as a contributor to DS cognitive impairment through PGE2 metabolism. Genetic normalization of Cbr1 copy number in Ts1Cje DS model mice, electrophysiology (hippocampal slice GABAB responses), behavioral memory testing, PGE2 measurement Scientific reports High 32843708
2021 Chrysin directly binds to CBR1 and inhibits its enzymatic activity; CBR1 inhibition increases cellular ROS, inducing ROS-dependent autophagy that degrades ferritin heavy chain (FTH1) and elevates free intracellular iron, triggering ferroptosis in pancreatic cancer cells; gemcitabine upregulates CBR1 (limiting ROS-mediated cytotoxicity), and CBR1 knockdown or chrysin sensitizes tumors to gemcitabine in vitro and in vivo. Direct binding assay (molecular and cellular levels), enzymatic activity assay, ROS measurement, autophagy and ferroptosis readouts (FTH1 degradation, iron levels, lipid peroxidation), siRNA knockdown, xenograft mouse model Biochemical pharmacology High 34673014
2022 Cinnamamide derivatives (1a, 1b containing 4-hydroxypiperidine) inhibit recombinant CBR1 enzymatic activity (confirmed by in vitro enzyme inhibition assay with molecular modeling); CBR1 inhibition by 1a/1b sensitizes A549 lung cancer cells to doxorubicin, reduces cancer cell migration, and alleviates menadione/doxorubicin-induced ROS and reduced glutathione in cardiomyoblasts, supporting CBR1 as a target for simultaneous chemosensitization and cardioprotection. Recombinant CBR1 enzyme inhibition assay, molecular docking, cell viability, apoptosis, ROS, migration (Transwell) assays Life sciences Medium 35792180
2024 CBR1 overexpression in NSCLC cells increases stemness markers (CD133-positive cells, OCT4, SOX2) and promotes quiescence (G0 phase cells, p27 expression); CBR1 inhibition (shRNA or PP-Me) reduces stemness, disrupts quiescence (increases cyclin D1, pRb), decreases SETD4 expression, and enhances cisplatin sensitivity; SETD4 overexpression rescues the chemosensitization caused by CBR1 inhibition, placing SETD4 downstream of CBR1. shRNA knockdown, pharmacological inhibition (PP-Me), overexpression, flow cytometry (G0 phase), Western blot (p27, cyclin D1, pRb, SETD4), xenograft mouse model Journal of Zhejiang University. Science. B Medium 41490728
2025 IGF2BP2, an m6A reader, stabilizes CBR1 mRNA in an m6A-dependent manner; IGF2BP2 silencing decreases CBR1 mRNA stability and activates PI3K/Akt/NF-κB signaling to promote inflammation in colitis; CBR1 overexpression counteracts the pro-inflammatory effect of IGF2BP2 knockdown, placing CBR1 downstream of IGF2BP2-mediated m6A RNA regulation as an anti-inflammatory effector. siRNA knockdown of IGF2BP2 in Caco-2 cells, m6A-dependent mRNA stability assay, PI3K/Akt/NF-κB pathway analysis by Western blot, CBR1 overexpression rescue, DSS-colitis mouse model International immunopharmacology Medium 40526983
2025 E2F2 transcriptionally activates miR-1290 by binding its promoter (validated by ChIP and dual-luciferase reporter assay); miR-1290 targets the 3'-UTR of CBR1 and suppresses its expression (validated by dual-luciferase assay); E2F2 knockdown increases CBR1, promotes hippocampal neurogenesis, and alleviates depressive behaviors in PSD rats; miR-1290 overexpression or CBR1 inhibition counteracts neurogenesis-promoting effects of E2F2 knockdown, establishing the E2F2→miR-1290⊣CBR1 axis. ChIP for E2F2 at miR-1290 promoter, dual-luciferase reporter for E2F2/miR-1290 and miR-1290/CBR1 3'-UTR interactions, E2F2 knockdown in PSD rat model, neurogenesis markers (NeuN, BDNF), rescue experiments Mammalian genome Medium 41310140
2025 Various anthracyclines show differential susceptibility to CBR1-mediated resistance in A549 lung cancer cells overexpressing CBR1: aclarubicin showed the greatest dependence on CBR1 overexpression for resistance despite low in vitro catalytic velocity with recombinant CBR1, indicating CBR1-mediated resistance involves mechanisms beyond simple carbonyl reduction rate for some anthracyclines. CBR1 transduction/overexpression in A549 cells, cytotoxicity assays with five anthracyclines, in vitro recombinant CBR1 enzyme kinetics Medical oncology Medium 40629205
2025 Vitamin K2 binds downstream target Nrf2, inhibits Keap1-mediated ubiquitination of Nrf2, and Nrf2 upregulates CBR1 to inhibit osteoblast ferroptosis caused by the inflammatory mediator PGE2; EMSA and ChIP-qPCR confirm Nrf2 binding to the CBR1 promoter, demonstrating a Vitamin K2→Nrf2→CBR1 protective axis against PGE2-induced osteoblast ferroptosis. Molecular docking, EMSA, ChIP-qPCR, metabolomics, transcriptomics, animal experiments, Nrf2/Keap1 ubiquitination assays Communications biology Medium 40721947
2024 In a Down syndrome mouse model (Ts65Dn), CBR1 activity is elevated and contributes to hypotension; pharmacological inhibition of CBR1 increases blood pressure in Ts65Dn mice; Cbr1 heterozygous null mice have reduced CBR1 activity and elevated blood pressure; underlying mechanisms include alterations in sympathetic tone and prostaglandin metabolism, establishing CBR1 as a regulator of blood pressure homeostasis. Telemetric blood pressure measurement in Ts65Dn DS model mice, CBR1 pharmacological inhibition, Cbr1 heterozygous null mice, CBR1 enzyme activity assays, prostaglandin measurement bioRxiv (preprint)preprint Medium

Source papers

Stage 0 corpus · 108 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Network organization of the human autophagy system. Nature 1286 20562859
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2000 The DNA sequence of human chromosome 21. Nature 808 10830953
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2003 A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling. Nature biotechnology 558 12577067
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2004 14-3-3-affinity purification of over 200 human phosphoproteins reveals new links to regulation of cellular metabolism, proliferation and trafficking. The Biochemical journal 372 14744259
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1981 Purification and properties of an NADPH-dependent carbonyl reductase from human brain. Relationship to prostaglandin 9-ketoreductase and xenobiotic ketone reductase. The Journal of biological chemistry 322 7005231
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2008 The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative. Chemico-biological interactions 315 19027726
2020 Phosphorylated tau interactome in the human Alzheimer's disease brain. Brain : a journal of neurology 290 32812023
2011 Anthracycline-related cardiomyopathy after childhood cancer: role of polymorphisms in carbonyl reductase genes--a report from the Children's Oncology Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 288 22124095
2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). Journal of proteome research 237 19199708
2014 Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset. Journal of proteomics 218 24769233
2013 Why do cellular proteins linked to K63-polyubiquitin chains not associate with proteasomes? The EMBO journal 213 23314748
2015 ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature 209 26618866
2009 Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis. Cell 208 19135240
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2020 Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Molecular cell 159 32416067
2009 Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6. Science signaling 159 20029029
2021 Chrysin induces autophagy-dependent ferroptosis to increase chemosensitivity to gemcitabine by targeting CBR1 in pancreatic cancer cells. Biochemical pharmacology 63 34673014
2008 In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: studies of the mode of action in Staphylococcus aureus. Antimicrobial agents and chemotherapy 58 18443108
2007 A functional genetic polymorphism on human carbonyl reductase 1 (CBR1 V88I) impacts on catalytic activity and NADPH binding affinity. Drug metabolism and disposition: the biological fate of chemicals 52 17344335
1993 Cbr, an algal homolog of plant early light-induced proteins, is a putative zeaxanthin binding protein. The Journal of biological chemistry 49 8407922
2008 In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: microbiology profiling studies with staphylococci and streptococci. Antimicrobial agents and chemotherapy 46 18443106
2001 Involvement of zeaxanthin and of the Cbr protein in the repair of photosystem II from photoinhibition in the green alga Dunaliella salina. Biochimica et biophysica acta 37 11779558
1998 Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved in Down syndrome. Genomics 35 9503011
2014 CBR antimicrobials alter coupling between the bridge helix and the β subunit in RNA polymerase. Nature communications 34 24598909
2007 Functional characterization of the promoter of human carbonyl reductase 1 (CBR1). Role of XRE elements in mediating the induction of CBR1 by ligands of the aryl hydrocarbon receptor. Molecular pharmacology 34 17569794
2012 Regulation of human carbonyl reductase 1 (CBR1, SDR21C1) gene by transcription factor Nrf2. Chemico-biological interactions 33 23247010
2008 Inhibition of polymorphic human carbonyl reductase 1 (CBR1) by the cardioprotectant flavonoid 7-monohydroxyethyl rutoside (monoHER). Pharmaceutical research 32 18449627
1993 Human carbonyl reductase (CBR) localized to band 21q22.1 by high-resolution fluorescence in situ hybridization displays gene dosage effects in trisomy 21 cells. Genomics 32 8432528
2015 CBR antimicrobials inhibit RNA polymerase via at least two bridge-helix cap-mediated effects on nucleotide addition. Proceedings of the National Academy of Sciences of the United States of America 31 26195788
2008 Pharmacogenetics of human carbonyl reductase 1 (CBR1) in livers from black and white donors. Drug metabolism and disposition: the biological fate of chemicals 31 19022938
2013 Cytochrome b5 reductase encoded by CBR1 is essential for a functional male gametophyte in Arabidopsis. The Plant cell 29 23995085
2014 Induction of PGF2α synthesis by cortisol through GR dependent induction of CBR1 in human amnion fibroblasts. Endocrinology 28 24654784
1993 High-resolution mapping of D16led-1, Gart, Gas-4, Cbr, Pcp-4, and Erg on distal mouse chromosome 16. Genomics 28 8406490
2010 Bicarbonate induces membrane reorganization and CBR1 and TRPV1 endocannabinoid receptor migration in lipid microdomains in capacitating boar spermatozoa. The Journal of membrane biology 26 21104238
2008 Analysis of the substrate-binding site of human carbonyl reductases CBR1 and CBR3 by site-directed mutagenesis. Chemico-biological interactions 26 19061875
2012 Induction of carbonyl reductase 1 (CBR1) expression in human lung tissues and lung cancer cells by the cigarette smoke constituent benzo[a]pyrene. Toxicology letters 25 22531821
2015 Structural Basis of Transcription Inhibition by CBR Hydroxamidines and CBR Pyrazoles. Structure (London, England : 1993) 23 26190576
2019 Catalytic Enantioselective Addition of an Allyl Group to Ketones Containing a Tri-, a Di-, or a Monohalomethyl Moiety. Stereochemical Control Based on Distinctive Electronic and Steric Attributes of C-Cl, C-Br, and C-F Bonds. Journal of the American Chemical Society 20 31553181
2015 Tat-CBR1 inhibits inflammatory responses through the suppressions of NF-κB and MAPK activation in macrophages and TPA-induced ear edema in mice. Toxicology and applied pharmacology 19 25818598
2022 PHGDH Inhibitor CBR-5884 Inhibits Epithelial Ovarian Cancer Progression via ROS/Wnt/β-Catenin Pathway and Plays a Synergistic Role with PARP Inhibitor Olaparib. Oxidative medicine and cellular longevity 18 36105480
2020 PGK1 inhibitor CBR-470-1 protects neuronal cells from MPP+. Aging 17 32649311
2016 Cbr1 is a Dph3 reductase required for the tRNA wobble uridine modification. Nature chemical biology 17 27694803
2020 Maternal 25-Hydroxyvitamin D Deficiency Promoted Metabolic Syndrome and Downregulated Nrf2/CBR1 Pathway in Offspring. Frontiers in pharmacology 15 32184720
2017 CBr4 promoted intramolecular aerobic oxidative dehydrogenative arylation of aldehydes: application in the synthesis of xanthones and fluorenones. Organic & biomolecular chemistry 15 28134379
2016 RACK1 promotes hepatocellular carcinoma cell survival via CBR1 by suppressing TNF-α-induced ROS generation. Oncology letters 15 28105239
2006 Nonadiabatic effects in C-Br bond scission in the photodissociation of bromoacetyl chloride. The Journal of chemical physics 15 17129101
1994 Isolation and complete sequence of CBR, a gene encoding a putative cytochrome b reductase in Saccharomyces cerevisiae. European journal of biochemistry 15 8307010
2022 Visible-Light-Induced 1,6-Enynes Triggered C-Br Bond Homolysis of Bromomalonates: Solvent-Controlled Divergent Synthesis of Carbonylated and Hydroxylated Benzofurans. The Journal of organic chemistry 14 35749743
2000 Light-harvesting complex II pigments and proteins in association with Cbr, a homolog of higher-plant early light-inducible proteins in the unicellular green alga Dunaliella. Planta 14 10872227
1992 Linkage mapping of the carbonyl reductase (CBR) gene on human chromosome 21 using a DNA polymorphism in the 3' untranslated region. Genomics 14 1612603
2019 Probing ultrafast C-Br bond fission in the UV photochemistry of bromoform with core-to-valence transient absorption spectroscopy. Structural dynamics (Melville, N.Y.) 13 31649963
2015 Molecular Characterization and Functional Analysis of Cytochrome b5 Reductase (CBR) Encoding Genes from the Carotenogenic Yeast Xanthophyllomyces dendrorhous. PloS one 13 26466337
2023 Dual C-Br Isotope Fractionation Indicates Distinct Reductive Dehalogenation Mechanisms of 1,2-Dibromoethane in Dehalococcoides- and Dehalogenimonas-Containing Cultures. Environmental science & technology 12 36700533
2019 Pseudomonas donghuensis HYS virulence towards Caenorhabditis elegans is regulated by the Cbr/Crc system. Scientific reports 12 31217473
2017 A CBR framework with gradient boosting based feature selection for lung cancer subtype classification. Computers in biology and medicine 12 28527352
1996 Possible Role of Cbr, an Algal Early-Light-Induced Protein, in Nonphotochemical Quenching of Chlorophyll Fluorescence. Plant physiology 12 12226269
2020 Flufenamic acid alleviates sepsis-induced lung injury by up-regulating CBR1. Drug development research 11 32542754
2024 Preclinical efficacy of CBR-5884 against epithelial ovarian cancer cells by targeting the serine synthesis pathway. Discover oncology 10 38733440
2022 Cinnamamide derivatives with 4-hydroxypiperidine moiety enhance effect of doxorubicin to cancer cells and protect cardiomyocytes against drug-induced toxicity through CBR1 inhibition mechanism. Life sciences 10 35792180
2018 Tandem radical cyclization of N-methacryloyl benzamides with CBr4 to construct brominated isoquinolinediones. Organic & biomolecular chemistry 10 30298897
2015 Suppression of F1 Male-Specific Lethality in Caenorhabditis Hybrids by cbr-him-8. G3 (Bethesda, Md.) 10 26721896
2014 Molecular characterization of an endophytic Phomopsisliquidambaris CBR-15 from Cryptolepis buchanani Roem. and impact of culture media on biosynthesis of antimicrobial metabolites. 3 Biotech 9 28324573
2012 Sex differences in improved efficacy of doxorubicin chemotherapy in Cbr1+/- mice. Anti-cancer drugs 9 22343424
2007 Cloning and expression study of a putative carotene biosynthesis related (cbr) gene from the halotolerant green alga Dunaliella salina. Molecular biology reports 9 17562223
2020 Impairment of spatial memory accuracy improved by Cbr1 copy number resumption and GABAB receptor-dependent enhancement of synaptic inhibition in Down syndrome model mice. Scientific reports 8 32843708
2024 The small molecule CBR-5884 inhibits the Candida albicans phosphatidylserine synthase. mBio 7 38587428
2016 Evidence for concerted ring opening and C-Br bond breaking in UV-excited bromocyclopropane. The Journal of chemical physics 7 27369520
1992 Localization of four human chromosome 21 genes--SOD1, ETS2, IFNAR, and CBR--to two different chromosomes in the marsupial species Macropus eugenii. Cytogenetics and cell genetics 6 1380419
2024 CBR-470-1 protects against cardiomyocyte death in ischaemia/reperfusion injury by activating the Nrf2-GPX4 cascade. Toxicology and applied pharmacology 5 39343043
2022 CBR1 decreases protein carbonyl levels via the ROS/Akt/CREB pathway to extend lifespan in the cotton bollworm, Helicoverpa armigera. The FEBS journal 5 36421037
2025 The antiarthritic effect of CBR-470-1 in hypoxic environment is to increase the level of NOD-like receptor family pyrin domain containing 3 ubiquitination by decreasing phosphoglycerate kinase 1 activity. Clinical and translational medicine 4 39731281
2023 Regulatory roles of CARD9-BCL10-Rac1 (CBR) signalome in islet β-cell function in health and metabolic stress: Is there room for MALT1? Biochemical pharmacology 4 37991197
2018 CBR1 rs9024 genotype status impacts the bioactivation of loxoprofen in human liver. Biopharmaceutics & drug disposition 4 29851133
2015 Characterization of the Canine Anthracycline-Metabolizing Enzyme Carbonyl Reductase 1 (cbr1) and the Functional Isoform cbr1 V218. Drug metabolism and disposition: the biological fate of chemicals 4 25918240
2021 Maternal, umbilical arterial metabolic levels and placental Nrf2/CBR1 expression in pregnancies with and without 25-hydroxyvitamin D deficiency. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 3 34232092
2018 Regulation of the sperm-to-oocyte transition in Caenorhabditis briggsae hermaphrodites by the Cbr-met-2 and Cbr-fem-3 genes. Molecular reproduction and development 3 29693773
2025 IGF2BP2 regulates inflammation in ulcerative colitis through N6-methyladenosine-dependent modulation of CBR1. International immunopharmacology 2 40526983
2025 Vitamin K2 inhibits PGE2-mediated osteoblast ferroptosis by upregulation of CBR1 via the Nrf2/Keap1 pathway. Communications biology 2 40721947
2021 The Reactions of 6-(Hydroxymethyl)-2,2-dimethyl-1-azaspiro[4.4]nonanes with Methanesulfonyl Chloride or PPh3-CBr4. Molecules (Basel, Switzerland) 2 34641544
2017 Three closely related 1-(naphthalen-2-yl)prop-2-en-1-ones: pseudosymmetry, disorder and supramoleular assembly mediated by C-H...π and C-Br...π interactions. Acta crystallographica. Section C, Structural chemistry 2 28157129
2012 DNA sequence variants in the carbonyl reductase 1 (cbr1) gene in seven breeds of Canis lupus familiaris. Genetics and molecular research : GMR 2 22614280
1999 Differential responses to different light spectral ranges of violaxanthin de-epoxidation and accumulation of Cbr, an algal homologue of plant early light inducible proteins, in two strains of Dunaliella. Plant physiology and biochemistry : PPB 2 10580288
2025 The Influence of CYP2B6, GSTP1, and SLCO1B1 Star Allele-Predicted Phenotypes and CBR1 Genetic Variants on Effectiveness Outcomes in Patients With Hepatocellular Carcinoma Receiving Doxorubicin via Transarterial Chemoembolization. Pharmacology research & perspectives 1 40405401
2025 Thio-iso-phthalamide pincer ligand-driven oxidative addition of a C-Br bond to gold(I): synthesis and studies of SCS-gold(III) pincer complexes. Dalton transactions (Cambridge, England : 2003) 1 40824177
2022 The Cbr-DPY-10(Arg92Cys) modification is a reliable co-conversion marker for CRISPR/Cas9 genome editing in Caenorhabditis briggsae. microPublication biology 1 35622509
2017 Association between CBR1 polymorphisms and NSCLC in the Chinese population. Oncology letters 1 29113280
2016 Transcriptional regulation of the canine carbonyl reductase 1 gene (cbr1) by the specificity protein 1 (Sp1). Gene 1 27506315
2025 Various anthracyclines exhibit differential cytotoxic effects related to CBR1-induced resistance in lung cancer cells. Medical oncology (Northwood, London, England) 0 40629205
2025 E2F2 inhibits hippocampal neurogenesis in poststroke depression rats via the miR-1290/CBR1 axis. Mammalian genome : official journal of the International Mammalian Genome Society 0 41310140
2025 Identification of GSR and CBR1 as biomarkers in HIV-associated emphysema through transcriptomic analysis. HIV medicine 0 41313200
2025 Depleting CBR1 increases chemosensitivity by reducing stemness and quiescence traits in non-small cell lung cancer. Journal of Zhejiang University. Science. B 0 41490728
2024 Sanger Sequencing Reveals Novel Variants in GLO-1, ACE, and CBR1 Genes in Patients of Early and Severe Diabetic Nephropathy. Medicina (Kaunas, Lithuania) 0 39336582
2018 Correction to: Retraction of: Tumor Protein D52-Like 2 Contributes to Proliferation of Breast Cancer Cells; 10.10.89/cbr.2014.1723Cancer Biother Radiopharm 2017;32(10):387. DOI: 10.1089/cbr.2014.1723.retract. Cancer biotherapy & radiopharmaceuticals 0 31329730
2018 Correction to: Retraction of: Tumor Protein D52-Like 2 Accelerates Gastric Cancer Cell Proliferation; 10..2014.17610.89/cbr6Cancer Biother Radiopharm 2017;32(10):388. DOI: 10.1089/cbr.2014.1766.retract. Cancer biotherapy & radiopharmaceuticals 0 31329731