Affinage

CDCA7L

Cell division cycle-associated 7-like protein · UniProt Q96GN5

Length
454 aa
Mass
52.2 kDa
Annotated
2026-06-09
100 papers in source corpus 10 papers cited in narrative 10 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDCA7L (also called R1/RAM2/JPO2) is a nuclear transcriptional repressor and c-Myc cofactor that links transcriptional control of monoamine oxidase genes to oncogenic proliferation and survival signaling (PMID:15654081, PMID:15994933). It was cloned through Sp1-binding sites in the MAO A core promoter and represses MAO A transcription by binding the promoter directly, competing with Sp1; the same Sp1-competition mechanism represses MAO B, and glucocorticoid signaling drives its cytosol-to-nucleus translocation to modulate this repression (PMID:15654081, PMID:20980443, PMID:16728402). Independently identified as a binding partner of the c-Myc NH2-terminal domain, CDCA7L co-localizes with and binds c-Myc, potentiates c-Myc transforming activity, and complements a transformation-defective Myc mutant, with its loss impairing colony formation in medulloblastoma cells (PMID:15994933). Within apoptotic and proliferative circuits, CDCA7L acts downstream of p38 kinase and Bcl-2 but upstream of caspase-3, and upstream of cyclin D1 and E2F1 in c-Myc-induced proliferation (PMID:16829576). CDCA7L is tethered to chromatin and stabilized by the transcriptional co-activator LEDGF/p75, binding the same PHAT/integrase-binding domain that engages HIV-1 integrase such that the two compete for LEDGF/p75; this association is required for CDCA7L chromatin loading and underlies a JPO2:LEDGF/p75 complex that promotes PI3K/AKT-driven metastasis in medulloblastoma (PMID:16735438, PMID:17669426, PMID:27013196). Its expression is elevated by a multiple myeloma risk allele at an upstream IRF4-bound enhancer, and CDCA7L supports myeloma cell proliferation and suppresses apoptosis (PMID:27882933).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2005 High

    Established CDCA7L's two foundational activities — that it is a sequence-specific transcriptional repressor of MAO A and an independent c-Myc cofactor — defining it as both a DNA-binding regulator and an oncogenic partner.

    Evidence Yeast one-hybrid via Sp1 sites with EMSA/ChIP/reporter for MAO A repression; yeast two-hybrid against MycNTD with transformation and RNAi assays for the Myc link

    PMID:15654081 PMID:15994933

    Open questions at the time
    • Direct DNA-binding domain of CDCA7L not mapped
    • Mechanism by which it potentiates Myc transformation (cofactor recruitment vs. target gene effects) unresolved
  2. 2006 High

    Connected CDCA7L's MAO A repression to upstream glucocorticoid signaling through ligand-induced nuclear translocation, showing its repressor activity is regulated rather than constitutive.

    Evidence Reporter assays, EMSA, shRNA knockdown, and immunofluorescence localization in neuroblastoma/glioblastoma cells

    PMID:16728402

    Open questions at the time
    • Signal transducing the dexamethasone cue to CDCA7L translocation not identified
    • Whether translocation involves post-translational modification unknown
  3. 2006 High

    Positioned CDCA7L within apoptotic and proliferative pathways by epistasis, placing it downstream of p38/Bcl-2 and upstream of caspase-3, cyclin D1, and E2F1, and confirming c-Myc induces its expression.

    Evidence Pharmacological inhibition, overexpression, siRNA, co-IP, and IHC in apoptosis and proliferation models

    PMID:16829576

    Open questions at the time
    • Direct molecular targets mediating caspase-3 and cyclin D1 effects not defined
    • Whether the apoptotic role is dependent on MAO A activity vs. independent transcriptional targets unresolved
  4. 2006 High

    Identified LEDGF/p75 as the factor that tethers CDCA7L to chromatin and stabilizes it, revealing how a repressor lacking strong autonomous chromatin retention is loaded onto chromosomes.

    Evidence In vitro and in vivo binding, domain mapping (aa 58–119), competition with recombinant integrase, live-cell co-localization, and protein stability assays

    PMID:16735438

    Open questions at the time
    • Functional consequence of chromatin tethering for specific target genes not tested
    • Genomic loci co-occupied by CDCA7L and LEDGF/p75 not mapped
  5. 2007 High

    Refined the CDCA7L–LEDGF/p75 interface and demonstrated functional competition with HIV-1 integrase, showing CDCA7L can interfere with viral replication and activate the HIV-1 LTR.

    Evidence Yeast two-hybrid, pull-down, AlphaScreen, co-IP, LEDGF/p75 mutagenesis, HIV-1 replication and LTR reporter assays

    PMID:17669426

    Open questions at the time
    • Physiological relevance of LTR activation by CDCA7L unclear
    • Distinct binding determinants on LEDGF/p75 for CDCA7L vs. integrase only partially mapped
  6. 2010 High

    Generalized the Sp1-competition repressor mechanism beyond MAO A to MAO B, establishing CDCA7L as a coordinated regulator of monoamine oxidase gene expression.

    Evidence Yeast one-hybrid, EMSA Sp1-competition, ChIP, and reporter assays on the MAO B promoter

    PMID:20980443

    Open questions at the time
    • Whether additional Sp1-driven promoters are targets not surveyed
    • Stoichiometry of CDCA7L vs. Sp1 occupancy in vivo not quantified
  7. 2011 Medium

    Provided in vivo human evidence for the CDCA7L–MAO A regulatory axis by correlating reduced CDCA7L with elevated MAO A in depressive disorder brain tissue.

    Evidence Western blot quantification and MAO A activity assay in postmortem prefrontal cortex with correlation analysis

    PMID:21654740

    Open questions at the time
    • Correlative/observational, not interventional
    • Causality and directionality in human brain not established
  8. 2016 High

    Defined the genetic and cellular basis of CDCA7L overexpression in multiple myeloma, linking an IRF4-bound enhancer risk allele to increased expression and a pro-proliferative, anti-apoptotic role.

    Evidence Chromatin conformation capture, IRF4 ChIP, reporter assays, and siRNA knockdown with proliferation/apoptosis readouts

    PMID:27882933

    Open questions at the time
    • Downstream effectors of CDCA7L driving myeloma proliferation not identified
    • Whether the Myc or LEDGF/p75 axis mediates the myeloma phenotype untested
  9. 2016 Medium

    Extended the JPO2:LEDGF/p75 complex to a metastatic function, showing CDCA7L drives medulloblastoma metastasis via feed-forward PI3K/AKT circuits.

    Evidence In vivo medulloblastoma metastasis model with overexpression, complex identification, and PI3K/AKT pathway readouts

    PMID:27013196

    Open questions at the time
    • Pathway circuit details from a single lab with limited orthogonal validation
    • Direct molecular link between CDCA7L and AKT activation not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CDCA7L's transcriptional repressor activity, its c-Myc cofactor function, and its LEDGF/p75-dependent chromatin tethering are mechanistically integrated into a single coherent activity remains unresolved.
  • No structure of CDCA7L or its complexes
  • Genome-wide direct target set not defined
  • Whether MAO repression and oncogenic cofactor roles share a common molecular surface unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2 GO:0005694 chromosome 1
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1643685 Disease 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-162582 Signal Transduction 1
Partners
MYCPSIP1SP1
Complex memberships
JPO2:LEDGF/p75 complex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 CDCA7L (R1/RAM2) was identified as a novel transcriptional repressor of the MAO A gene. It was cloned by yeast one-hybrid screening using Sp1-binding sites in the MAO A core promoter. Transfection of R1 in neuroblastoma cells inhibited MAO A promoter and enzymatic activity in a dose-dependent manner. Gel-shift assay showed endogenous R1 protein interacted with the R1 binding sequence, and ChIP confirmed direct binding to the natural MAO A promoter in vivo. Immunocytochemical analysis showed R1 is expressed in both cytosol and nucleus. Yeast one-hybrid screen, luciferase reporter assay, gel-shift/EMSA, chromatin immunoprecipitation (ChIP), immunocytochemistry, transfection overexpression The Journal of biological chemistry High 15654081
2006 Glucocorticoid (dexamethasone) induces time-dependent translocation of CDCA7L (R1) from the cytosol to the nucleus in neuroblastoma and glioblastoma cells, but not in R1 knockdown cells. R1 interacts with Sp1-binding sites in the MAO A promoter and represses MAO A gene expression. Glucocorticoid receptor interacts indirectly with the MAO A promoter via Sp1 or R1. Androgen receptor interacts with Sp1 but not R1 on Sp1 sites, revealing differential regulation. Luciferase reporter assay, gel-shift/EMSA, shRNA knockdown, immunofluorescence/immunocytochemistry for subcellular localization The Journal of biological chemistry High 16728402
2006 In serum starvation-induced apoptosis, R1 (CDCA7L/JPO2) protein levels are reduced while MAO A and caspase-3 are increased. Using p38 kinase inhibitor, R1 overexpression, and MAO A inhibitor, R1 and MAO A were positioned downstream of p38 kinase and Bcl-2 but upstream of caspase-3 in the apoptotic signaling pathway. Immunoprecipitation and immunohistochemistry demonstrated that c-Myc co-localizes with R1 and induces R1 gene expression. R1 and MAO A were shown to act upstream of cyclin D1 and E2F1 in c-Myc-induced proliferative signaling. Pharmacological inhibition (p38 inhibitor, MAO A inhibitor), overexpression, siRNA knockdown, co-immunoprecipitation, immunohistochemistry, western blot Proceedings of the National Academy of Sciences of the United States of America High 16829576
2006 CDCA7L (JPO2) associates with transcriptional co-activator p75 (LEDGF/p75) both in vitro and in vivo. The PHAT domain of p75, which mediates its interaction with HIV-1 integrase, also mediates interaction with JPO2. Recombinant integrase competes with JPO2 for binding to p75 in vitro (mutually competitive). JPO2 binds p75 through a 61-residue region (amino acids 58–119) distinct from its Myc-interacting domain. In cells, JPO2 and p75 co-localize throughout the cell cycle and concentrate on condensed chromosomes during mitosis. JPO2 association with chromatin strictly depends upon p75, and p75 stabilizes intracellular steady-state levels of JPO2. In vitro binding assay, co-immunoprecipitation, competitive binding with recombinant proteins, domain mapping, live-cell co-localization (fluorescence microscopy), protein stability assay Journal of cell science High 16735438
2005 CDCA7L (JPO2) was identified as a novel c-Myc NH2-terminal domain (MycNTD) binding protein by two-hybrid screening of a medulloblastoma cDNA library. JPO2 shows nuclear co-localization with c-Myc and interacts with c-Myc both in vitro and in mammalian cells. In Rat1a transformation assays, JPO2 potentiates c-Myc transforming activity and can complement a transformation-defective Myc mutant. RNAi-mediated JPO2 knockdown impairs colony formation in medulloblastoma cells. Yeast two-hybrid screen, in vitro binding, co-immunoprecipitation, immunofluorescence co-localization, Rat1a transformation assay, RNAi knockdown/colony formation assay Cancer research High 15994933
2007 JPO2 (CDCA7L) was identified as a binding partner of the C-terminal integrase-binding domain (IBD) of LEDGF/p75 by yeast two-hybrid screening. Specific interaction was verified by pull-down, AlphaScreen, and co-immunoprecipitation. Competition assays using recombinant proteins showed mutually exclusive binding of either JPO2 or HIV-1 integrase to LEDGF/p75. Notably, JPO2 retains binding to certain LEDGF/p75 mutants (I365A, D366A, F406A) that are totally defective for HIV-1 integrase interaction, indicating different binding mechanisms. JPO2 overexpression caused modest but reproducible inhibition of HIV-1 replication, consistent with competition for LEDGF/p75. JPO2 overexpression also activated transcription from the HIV-1 LTR. Yeast two-hybrid screen, pull-down, AlphaScreen, co-immunoprecipitation, competition assay with recombinant proteins, site-directed mutagenesis of LEDGF/p75, HIV-1 replication assay, LTR-driven reporter assay Journal of molecular biology High 17669426
2010 CDCA7L (R1/RAM2/JPO2) was identified as a novel transcriptional repressor of MAO B using Sp1-binding motifs as bait in a yeast one-hybrid screen. EMSA demonstrated that R1 competed with Sp1 for binding to the Sp1 site in the MAO B promoter in vitro. R1 reduced Sp1-activated glucocorticoid activation of MAO B promoter activity. ChIP analysis showed lower occupancy by R1 at the MAO B core promoter in response to dexamethasone. Yeast one-hybrid screen, EMSA, luciferase reporter assay, chromatin immunoprecipitation (ChIP) Molecular pharmacology High 20980443
2016 A multiple myeloma risk SNP (rs4487645 G>T) resides in an enhancer element 47 kb upstream of CDCA7L. The G-risk allele increases IRF4 binding at the enhancer, which interacts with the CDCA7L promoter by chromatin looping. The G allele is associated with increased CDCA7L expression. Suppression of CDCA7L limits myeloma cell proliferation through apoptosis. Genetic association + functional characterization: chromatin conformation capture (enhancer-promoter interaction), IRF4 ChIP, reporter assay, siRNA knockdown with proliferation/apoptosis readout Nature communications High 27882933
2016 JPO2 (CDCA7L) and its partner LEDGF/p75 are critical modulators of PI3K/AKT signaling and metastasis in medulloblastoma. JPO2 overexpression induced metastatic medulloblastoma in vivo. Two synergistic feed-forward regulatory circuits involving LEDGF/p75 and AKT were identified as promoting metastatic phenotypes downstream of JPO2. In vivo medulloblastoma metastasis model, overexpression, identification of JPO2:LEDGF/p75 protein complex, pathway analysis (PI3K/AKT signaling readouts) Cancer research Medium 27013196
2011 R1 (CDCA7L/JPO2) protein levels are significantly reduced by ~37.5% in postmortem prefrontal cortex of untreated MDD subjects compared to controls, and this reduction is significantly correlated with an approximately 40% increase in MAO A protein levels and MAO A catalytic activity within the same MDD groups. This supports an in vivo regulatory relationship between R1 and MAO A. Western blot quantification of postmortem human brain tissue, MAO A catalytic activity assay, correlation analysis Neuropsychopharmacology Medium 21654740

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 TNF-R1 signaling: a beautiful pathway. Science (New York, N.Y.) 1495 12040173
1994 Structure of ribonucleotide reductase protein R1. Nature 459 8052308
2013 Using high-resolution quantitative mapping of R1 as an index of cortical myelination. NeuroImage 278 23756203
2002 The starch-related R1 protein is an alpha -glucan, water dikinase. Proceedings of the National Academy of Sciences of the United States of America 216 12011472
2017 Arbuscular mycorrhiza-specific enzymes FatM and RAM2 fine-tune lipid biosynthesis to promote development of arbuscular mycorrhiza. The New phytologist 210 28380681
1990 S-phase-specific expression of mammalian ribonucleotide reductase R1 and R2 subunit mRNAs. Biochemistry 168 1696835
1991 RAM2, an essential gene of yeast, and RAM1 encode the two polypeptide components of the farnesyltransferase that prenylates a-factor and Ras proteins. Proceedings of the National Academy of Sciences of the United States of America 162 1763050
1999 Spatial distribution of GABA(B)R1 receptor mRNA and binding sites in the rat brain. The Journal of comparative neurology 159 10440706
1991 Retrotransposable elements R1 and R2 interrupt the rRNA genes of most insects. Proceedings of the National Academy of Sciences of the United States of America 157 1849649
1993 Protein chemical characterization and immunocytochemical localization of the NMDA receptor subunit NMDA R1. The Journal of biological chemistry 149 8226775
2019 Notoginsenoside R1 Ameliorates Diabetic Retinopathy through PINK1-Dependent Activation of Mitophagy. Cells 141 30832367
2002 The IrrE protein of Deinococcus radiodurans R1 is a novel regulator of recA expression. Journal of bacteriology 140 12399492
1990 Type I (R1) and type II (R2) ribosomal DNA insertions of Drosophila melanogaster are retrotransposable elements closely related to those of Bombyx mori. Journal of molecular biology 134 1690812
2006 Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway. Proceedings of the National Academy of Sciences of the United States of America 132 16829576
2006 Glucocorticoid and androgen activation of monoamine oxidase A is regulated differently by R1 and Sp1. The Journal of biological chemistry 120 16728402
2006 Transcriptional co-activator p75 binds and tethers the Myc-interacting protein JPO2 to chromatin. Journal of cell science 103 16735438
2017 Paclitaxel Reduces Axonal Bclw to Initiate IP3R1-Dependent Axon Degeneration. Neuron 97 29024661
2005 Plasmid R1--replication and its control. Plasmid 95 16199086
2004 Preserving genome integrity: the DdrA protein of Deinococcus radiodurans R1. PLoS biology 91 15361932
2002 Cloning and functional expression of the first Drosophila melanogaster sulfakinin receptor DSK-R1. Biochemical and biophysical research communications 91 11846406
2017 N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death. Cell death and differentiation 79 28186505
1975 Analysis of early adenovirus 2 RNA using Eco R-R1 viral DNA fragments. Journal of virology 78 1142475
2020 Focus on Notoginsenoside R1 in Metabolism and Prevention Against Human Diseases. Drug design, development and therapy 73 32103897
1995 Gene 19 of plasmid R1 is required for both efficient conjugative DNA transfer and bacteriophage R17 infection. Journal of bacteriology 72 7543471
2014 Notoginsenoside R1 attenuates experimental inflammatory bowel disease via pregnane X receptor activation. The Journal of pharmacology and experimental therapeutics 70 25472953
1993 Sequence relationship of retrotransposable elements R1 and R2 within and between divergent insect species. Molecular biology and evolution 70 8383793
2007 Differential interaction of HIV-1 integrase and JPO2 with the C terminus of LEDGF/p75. Journal of molecular biology 68 17669426
2005 Identification of a novel c-Myc protein interactor, JPO2, with transforming activity in medulloblastoma cells. Cancer research 67 15994933
2018 Notoginsenoside R1 ameliorates diabetic encephalopathy by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation. Oncotarget 66 29507694
1997 Expression of corticotropin-releasing hormone and its R1 receptor in human endometrial stromal cells. The Journal of clinical endocrinology and metabolism 66 9141555
2010 Notoginsenoside R1 attenuates renal ischemia-reperfusion injury in rats. Shock (Augusta, Ga.) 65 20023602
2018 Notoginsenoside R1 Protects Against Diabetic Cardiomyopathy Through Activating Estrogen Receptor α and Its Downstream Signaling. Frontiers in pharmacology 64 30450046
2011 The reduction of R1, a novel repressor protein for monoamine oxidase A, in major depressive disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 64 21654740
2005 The R1 resistance gene cluster contains three groups of independently evolving, type I R1 homologues and shows substantial structural variation among haplotypes of Solanum demissum. The Plant journal : for cell and molecular biology 63 16167894
2020 High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection. Cancers 61 33036243
2013 RAM1 and RAM2 function and expression during arbuscular mycorrhizal symbiosis and Aphanomyces euteiches colonization. Plant signaling & behavior 58 24270627
2015 Immune activation mediated by the late blight resistance protein R1 requires nuclear localization of R1 and the effector AVR1. The New phytologist 56 25760731
2021 Notoginsenoside R1 attenuates oxidative stress-induced osteoblast dysfunction through JNK signalling pathway. Journal of cellular and molecular medicine 55 34786818
2005 R1, a novel repressor of the human monoamine oxidase A. The Journal of biological chemistry 55 15654081
1997 Sok antisense RNA from plasmid R1 is functionally inactivated by RNase E and polyadenylated by poly(A) polymerase I. Molecular microbiology 55 9383156
2014 Notoginsenoside R1 attenuates atherosclerotic lesions in ApoE deficient mouse model. PloS one 53 24933211
1992 CDC43 and RAM2 encode the polypeptide subunits of a yeast type I protein geranylgeranyltransferase. The Journal of biological chemistry 53 1400380
1997 Cloning and characterization of the R1 and R2 subunits of ribonucleotide reductase from Trypanosoma brucei. Proceedings of the National Academy of Sciences of the United States of America 51 9192674
1998 Galanin-R1 receptor in anterior and mid-hypothalamus: distribution and regulation. The Journal of comparative neurology 50 9733081
2018 Structure and Analysis of R1 and R2 Pyocin Receptor-Binding Fibers. Viruses 48 30110933
2013 DdrA, DdrD, and PprA: components of UV and mitomycin C resistance in Deinococcus radiodurans R1. PloS one 47 23840905
2002 Microscopic (R1) and macroscopic (R2) residual disease in patients with resected non-small cell lung cancer. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 46 11932154
2019 Palmitoylation is required for TNF-R1 signaling. Cell communication and signaling : CCS 45 31382980
1991 Repression and derepression of conjugation of plasmid R1 by wild-type and mutated finP antisense RNA. Molecular microbiology 44 1707476
2006 Chromatin structure and transcription of the R1- and R2-inserted rRNA genes of Drosophila melanogaster. Molecular and cellular biology 43 17000772
2011 An activation domain of plasmid R1 TraI protein delineates stages of gene transfer initiation. Molecular microbiology 41 22066957
2014 Genome-wide transcriptome and antioxidant analyses on gamma-irradiated phases of deinococcus radiodurans R1. PloS one 40 24465634
2002 Rates of R1 and R2 retrotransposition and elimination from the rDNA locus of Drosophila melanogaster. Genetics 40 12399390
1999 Identification of the R1 oncogene and its protein product from the rhadinovirus of rhesus monkeys. Journal of virology 39 10233975
1994 Expression of the NMDA R1 receptor in selected human brain regions. Neuroreport 39 8061305
2019 Notoginsenoside R1 (NGR1) Attenuates Chronic Atrophic Gastritis in Rats. Medical science monitor : international medical journal of experimental and clinical research 38 30757999
2010 Transcription factor E2F-associated phosphoprotein (EAPP), RAM2/CDCA7L/JPO2 (R1), and simian virus 40 promoter factor 1 (Sp1) cooperatively regulate glucocorticoid activation of monoamine oxidase B. Molecular pharmacology 37 20980443
1999 Metastable structures and refolding kinetics in hok mRNA of plasmid R1. RNA (New York, N.Y.) 36 10580469
2021 Orthopedic surgery-induced cognitive dysfunction is mediated by CX3CL1/R1 signaling. Journal of neuroinflammation 35 33858422
2020 Notoginsenoside R1 functionalized gelatin hydrogels to promote reparative dentinogenesis. Acta biomaterialia 33 33348063
2009 Plasmid r1 conjugative DNA processing is regulated at the coupling protein interface. Journal of bacteriology 33 19767437
2007 Gene and cell survival: lessons from prokaryotic plasmid R1. EMBO reports 32 17471262
1998 Degradation pathway of CopA, the antisense RNA that controls replication of plasmid R1. Microbiology (Reading, England) 32 9695924
2013 miR-449a contributes to glucocorticoid-induced CRF-R1 downregulation in the pituitary during stress. Molecular endocrinology (Baltimore, Md.) 31 23893957
1993 Structure and promoter characterization of the gene encoding the large subunit (R1 protein) of mouse ribonucleotide reductase. Proceedings of the National Academy of Sciences of the United States of America 31 8248246
2019 Notoginsenoside R1 for Organs Ischemia/Reperfusion Injury: A Preclinical Systematic Review. Frontiers in pharmacology 30 31680976
2016 Multiple myeloma risk variant at 7p15.3 creates an IRF4-binding site and interferes with CDCA7L expression. Nature communications 29 27882933
2003 Adenovirus-mediated ribonucleotide reductase R1 gene therapy of human colon adenocarcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 29 14555530
2020 Notoginsenoside R1 activates the Ang2/Tie2 pathway to promote angiogenesis. Phytomedicine : international journal of phytotherapy and phytopharmacology 28 32823242
2017 Sequence of the R1 plasmid and comparison to F and R100. Plasmid 28 28359666
2009 Human monomeric antibody fragments to TRAIL-R1 and TRAIL-R2 that display potent in vitro agonism. mAbs 28 20068388
1993 TraM of plasmid R1 regulates its own expression. Molecular microbiology 28 8469119
2021 Lipase from Rhizopus oryzae R1: in-depth characterization, immobilization, and evaluation in biodiesel production. Journal, genetic engineering & biotechnology 27 33400043
2019 Notoginsenoside R1 alleviates lipopolysaccharide-triggered PC-12 inflammatory damage via elevating microRNA-132. Artificial cells, nanomedicine, and biotechnology 27 31062615
2019 Notoginsenoside R1: A systematic review of its pharmacological properties. Die Pharmazie 27 31739829
2016 Notoginsenoside R1 significantly promotes in vitro osteoblastogenesis. International journal of molecular medicine 27 27352906
2003 GABAB receptor subunits, R1 and R2, in brainstem catecholamine and serotonin neurons. Brain research 27 12706246
1991 The TraM protein of plasmid R1 is a DNA-binding protein. Molecular microbiology 27 2041477
2022 Notoginsenoside R1 Ameliorates Cardiac Lipotoxicity Through AMPK Signaling Pathway. Frontiers in pharmacology 26 35370720
2019 Glutathione-glutaredoxin is an efficient electron donor system for mammalian p53R2-R1-dependent ribonucleotide reductase. The Journal of biological chemistry 25 31266802
2016 Conjugative DNA Transfer Is Enhanced by Plasmid R1 Partitioning Proteins. Frontiers in molecular biosciences 25 27486582
2009 Protein and DNA effectors control the TraI conjugative helicase of plasmid R1. Journal of bacteriology 25 19767439
2021 Notoginsenoside R1 attenuates breast cancer progression by targeting CCND2 and YBX3. Chinese medical journal 24 33480613
2015 Interaction between RING1 (R1) and the Ubiquitin-like (UBL) Domains Is Critical for the Regulation of Parkin Activity. The Journal of biological chemistry 24 26631732
2003 RAM2: an essential gene in the prenylation pathway of Candida albicans. Microbiology (Reading, England) 24 12576598
2019 The role of G-quadruplex structures of LIGS-generated aptamers R1.2 and R1.3 in IgM specific recognition. International journal of biological macromolecules 23 31022491
1994 Regulation of mammalian ribonucleotide reductase R1 mRNA stability is mediated by a ribonucleotide reductase R1 mRNA 3'-untranslated region cis-trans interaction through a protein kinase C-controlled pathway. The Biochemical journal 23 8067998
2019 In Vitro Anti-hepatoma Activities of Notoginsenoside R1 Through Downregulation of Tumor Promoter miR-21. Digestive diseases and sciences 22 31559550
2018 Interferons type II and their receptors R1 and R2 in fish species: Evolution, structure, and function. Fish & shellfish immunology 22 29742458
2007 Expression profiling identifies the CRH/CRH-R1 system as a modulator of neurovascular gene activity. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 22 17293846
2000 Activation of lymphocyte signaling by the R1 protein of rhesus monkey rhadinovirus. Journal of virology 22 10684288
1997 Evolution of R1 and R2 in the rDNA units of the genus Drosophila. Genetica 22 9440258
1993 Expression of gene 19 of the conjugative plasmid R1 is controlled by RNase III. Molecular microbiology 22 7694035
2016 JPO2/CDCA7L and LEDGF/p75 Are Novel Mediators of PI3K/AKT Signaling and Aggressive Phenotypes in Medulloblastoma. Cancer research 21 27013196
2015 TRAIL-receptor preferences in pancreatic cancer cells revisited: Both TRAIL-R1 and TRAIL-R2 have a licence to kill. BMC cancer 21 26138346
2009 Impact of TNF-R1 and CD95 internalization on apoptotic and antiapoptotic signaling. Results and problems in cell differentiation 21 19132322
2009 TRAIL-R1 polymorphisms and cancer susceptibility: an evidence-based meta-analysis. European journal of cancer (Oxford, England : 1990) 21 19643596
2002 Cloning and characterization of rhesus monkey MCH-R1 and MCH-R2. Peptides 21 12182940
2007 Maternal and umbilical sTNF-R1 in preeclamptic pregnancies with intrauterine normal and growth retarded fetus. Hypertension in pregnancy 20 17454214
2006 Functional expression of TRAIL receptors TRAIL-R1 and TRAIL-R2 in esophageal adenocarcinoma. European journal of cancer (Oxford, England : 1990) 20 16426839

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