Affinage

DKK3

Dickkopf-related protein 3 · UniProt Q9UBP4

Length
350 aa
Mass
38.4 kDa
Annotated
2026-04-28
100 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DKK3 (also known as REIC) is a secreted, N-glycosylated Wnt pathway modulator that functions as a tumor suppressor by antagonizing beta-catenin nuclear translocation and activating stress-induced apoptotic signaling. Extracellularly, DKK3 inhibits Wnt/beta-catenin/TCF-4 signaling, reducing expression of targets such as c-Myc and cyclin D1, and physically binds ASK1 to suppress downstream JNK/p38 activation in contexts including hepatic metabolism and neuroinflammation (PMID:18048388, PMID:27016281, PMID:35658977). An intracellular isoform (Dkk3b) sequesters unphosphorylated beta-catenin with beta-TrCP in the cytoplasm, preventing its nuclear entry and arresting proliferation (PMID:28738084). Overexpression in cancer cells triggers ER stress–dependent, JNK/caspase-mediated apoptosis—with resistance conferred by the ER chaperone BiP—while the secreted protein also drives monocyte-to-dendritic-cell differentiation through STAT1/3 and GSK-3beta phosphorylation, and the DKK3 promoter is frequently silenced in tumors by DNA hypermethylation (PMID:19626590, PMID:19212670, PMID:11814687).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 Medium

    Initial characterization established that REIC/DKK3 expression is cell-cycle regulated and that its exogenous expression inhibits tumor cell growth, raising the question of whether it acts as a tumor suppressor.

    Evidence Cell cycle synchronization, northern blot, and exogenous expression in tumor cells

    PMID:11708809

    Open questions at the time
    • No mechanism for growth inhibition identified
    • Downstream signaling pathway unknown
    • Expression regulation unexplored
  2. 2002 High

    The mechanism of DKK3 silencing in cancer was resolved as promoter hypermethylation, explaining its frequent downregulation in tumors and establishing it as an epigenetically regulated tumor suppressor.

    Evidence Methylation-specific PCR, bisulfite sequencing, and 5-aza-deoxycytidine demethylation restoring expression across multiple tumor lines

    PMID:11814687

    Open questions at the time
    • Whether methylation is the sole silencing mechanism was not addressed
    • Upstream signals driving methylation unknown
  3. 2004 Medium

    Biochemical characterization revealed two DKK3 isoforms (55 kDa cytosolic and 50 kDa secreted) with N-glycosylation, and showed that ectopic expression induces apoptosis and suppresses xenograft tumor growth, establishing a direct tumor-suppressive function.

    Evidence Ectopic expression in multiple cell lines, colony formation, xenograft in nude mice, biochemical analysis

    PMID:15516983

    Open questions at the time
    • Apoptotic signaling pathway not dissected
    • Functional distinction between the two isoforms unresolved
  4. 2007 High

    Two studies placed DKK3 in defined signaling pathways: it inhibits Wnt/beta-catenin/TCF-4 signaling (reducing nuclear beta-catenin, c-Myc, and cyclin D1) and activates JNK-dependent apoptosis in cancer cells, resolving the long-standing question of its downstream effectors.

    Evidence siRNA and overexpression with TCF-4 reporter assays and immunofluorescence (lung cancer); adenoviral overexpression with JNK inhibitor epistasis (testicular cancer)

    PMID:17273781 PMID:18048388

    Open questions at the time
    • Whether Wnt inhibition and JNK activation are linked or independent pathways was unclear
    • Receptor for DKK3 not identified
  5. 2009 High

    The mechanism of DKK3-induced apoptosis was refined to involve ER stress via IRE1alpha–ASK1–p38, and the secreted protein was shown to drive monocyte-to-dendritic-cell differentiation through STAT1/3 activation, revealing both cell-autonomous and immune-mediated tumor-suppressive arms.

    Evidence Adenoviral overexpression in fibroblasts with IRE1alpha/ASK1/p38 pathway analysis and IL-7 antibody neutralization; recombinant DKK3 protein on monocytes with STAT phosphorylation and in vivo immune cell accumulation

    PMID:19212670 PMID:19279003

    Open questions at the time
    • DKK3 receptor mediating monocyte differentiation unknown
    • Whether ER stress pathway operates in all cancer types not established
  6. 2010 Medium

    The ER chaperone BiP/GRP78 was identified as a key determinant of resistance to DKK3-induced apoptosis, confirming the centrality of ER stress in DKK3's pro-apoptotic mechanism.

    Evidence Resistant clone isolation, BiP siRNA knockdown sensitizing resistant cells to DKK3-induced apoptosis in vitro and in vivo

    PMID:19626590

    Open questions at the time
    • Whether DKK3 directly triggers unfolded protein response or acts indirectly unknown
    • Structural basis for DKK3-ER stress interaction unresolved
  7. 2012 Medium

    Antibody-blocking experiments demonstrated that secreted DKK3 acts at the cell surface to downregulate beta-catenin, Akt, and S6K signaling and induce G1 arrest, establishing that a receptor-mediated extracellular mechanism contributes to its tumor-suppressive function.

    Evidence Recombinant DKK3 protein treatment with anti-REIC antibody block, combined with overexpression and siRNA in gastric cancer cells

    PMID:22421143

    Open questions at the time
    • Identity of the cell-surface receptor not determined
    • Relationship between beta-catenin and Akt arm inhibition unclear
  8. 2015 High

    Two advances defined DKK3 function in new contexts: in dilated cardiomyopathy mouse models, Dkk3 shifts the balance from non-canonical (JNK/CAMKII) to canonical Wnt signaling, and the C-terminal cysteine-rich domain (C17-REIC) was mapped as sufficient for monocyte-to-DC differentiation and GSK-3beta phosphorylation.

    Evidence Transgenic and knockout mice crossed with DCM model with bidirectional molecular readouts; recombinant truncated domain analysis with monocyte differentiation and signaling assays

    PMID:25823913 PMID:26641069

    Open questions at the time
    • How DKK3 discriminates between canonical and non-canonical Wnt arms mechanistically unknown
    • No structural model for C17-REIC domain activity
  9. 2016 High

    DKK3 was shown to physically bind ASK1 and inhibit downstream P38/JNK signaling in hepatocytes, with epistasis using dominant-negative and constitutively active ASK1 confirming ASK1 as the direct effector mediating DKK3's metabolic protective functions.

    Evidence Co-immunoprecipitation of DKK3–ASK1, hepatocyte-specific KO and OE mice, epistasis with ASK1 mutants, metabolic phenotyping

    PMID:27016281

    Open questions at the time
    • Binding interface and stoichiometry of DKK3–ASK1 interaction uncharacterized
    • Whether DKK3–ASK1 interaction operates in all DKK3-expressing tissues unknown
  10. 2017 Medium

    Discovery of the Dkk3b isoform originating from intron 2 resolved the intracellular mechanism: Dkk3b captures unphosphorylated beta-catenin with beta-TrCP in the cytoplasm, preventing nuclear translocation and proliferation.

    Evidence Novel transcription start site mapping, co-immunoprecipitation of Dkk3b with beta-catenin and beta-TrCP, nuclear fractionation, proliferation assays

    PMID:28738084

    Open questions at the time
    • Dkk3b-beta-catenin-beta-TrCP complex validated only by Co-IP without reciprocal pulldown or in vitro reconstitution
    • Relative contribution of Dkk3b vs. secreted DKK3 in vivo not delineated
  11. 2022 Medium

    DKK3 was placed upstream of ASK1/JNK/p38 in microglia via Kremen-1 and DVL-1, with siRNA epistasis showing these receptors are required for DKK3's inhibitory effects on microglial M1 polarization and neuropathic pain.

    Evidence Intrathecal DKK3 injection with Kremen-1 and DVL-1 siRNA knockdown, behavioral testing, western blot, and immunofluorescence in SNI rats

    PMID:35658977

    Open questions at the time
    • Whether DKK3 directly binds Kremen-1 not demonstrated by direct binding assay
    • Relevance to human neuropathic pain not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the primary cell-surface receptor for secreted DKK3 remains unresolved: unlike other DKK family members, DKK3 does not bind canonical LRP5/6 co-receptors with high affinity, and whether Kremen-1 is a direct receptor or acts indirectly is unknown.
  • No high-affinity receptor identified by direct binding assay
  • Structural basis for DKK3 selectivity within the DKK family unknown
  • Integrated model reconciling ER stress, Wnt inhibition, and ASK1 binding in a unified signaling framework is lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140313 molecular sequestering activity 1
Localization
GO:0005576 extracellular region 4 GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-5357801 Programmed Cell Death 4 R-HSA-168256 Immune System 2
Partners
ASK1BTRCCTNNB1DVL1HSPA5KREMEN1

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 DKK3/REIC protein exists as two isoforms (55 kDa cytosolic and 50 kDa secreted), is N-glycosylated, and ectopic expression induces apoptosis and suppresses tumor growth in vitro and in vivo. Ectopic expression in HeLa, Hep3B, Huh7 cells; colony formation assay; xenograft in nude mice; biochemical characterization Oncogene Medium 15516983
2001 REIC/DKK3 expression is cell-cycle regulated (lowest in late G1 phase), and exogenous expression inhibits tumor cell growth, consistent with a tumor suppressor role. Cell cycle synchronization, northern blot, exogenous gene expression in tumor cells Biochemical and biophysical research communications Medium 11708809
2002 DKK3/REIC gene downregulation in tumor cells is caused by promoter hypermethylation; treatment with 5-aza-deoxycytidine restores expression, confirming epigenetic silencing as the mechanism. Methylation-specific PCR, bisulfite sequencing, 5-aza-deoxycytidine demethylation treatment Gene High 11814687
2007 DKK3 downregulation in lung cancer activates Wnt/beta-catenin/TCF-4 signaling; ectopic DKK3 expression inhibits TCF-4 activity, nuclear beta-catenin accumulation, and expression of TCF-4 targets c-Myc and cyclin D1; DKK3 siRNA knockdown promotes beta-catenin nuclear translocation. Ectopic expression, siRNA knockdown, TCF-4 reporter assay, immunofluorescence for nuclear beta-catenin, western blot for c-Myc and cyclin D1 Carcinogenesis High 18048388
2007 In testicular cancer cells, DKK3/REIC overexpression via adenovirus activates JNK signaling, leading to apoptosis; a JNK inhibitor abrogates this apoptosis, placing JNK downstream of DKK3. Adenoviral overexpression, JNK inhibitor treatment, apoptosis assay, xenograft model International journal of molecular medicine Medium 17273781
2008 In glioblastoma cells, DKK3/REIC transfection induces apoptosis through activation of phospho-JNK, caspase-9, and caspase-3, and reduction of beta-catenin; DKK3 knockdown augments cell growth. Transfection, siRNA knockdown, western blot for phospho-JNK/caspase-9/caspase-3/beta-catenin, apoptosis assay Neuro-oncology Medium 18443132
2009 DKK3/REIC overexpression in normal human fibroblasts triggers ER stress-mediated IL-7 production through the IRE1alpha–ASK1–p38–IRF-1 pathway; this IL-7 production mediates indirect anti-tumor effects when fibroblasts are co-transplanted with cancer cells. Adenoviral overexpression, IL-7 ELISA, IL-7 antibody neutralization, co-transplantation xenograft, western blot for IRE1alpha/ASK1/p38/IRF-1 The Journal of biological chemistry High 19279003
2009 Recombinant DKK3/REIC secreted protein induces differentiation of human CD14+ monocytes into a dendritic cell-like phenotype and activates STAT1 and STAT3 phosphorylation; intratumoral DKK3 protein administration suppresses tumor growth with accumulation of CD11c+ and CD8+ cells. Recombinant protein treatment of monocytes, flow cytometry, STAT phosphorylation western blot, intratumoral protein injection in mice International journal of oncology Medium 19212670
2010 BiP/GRP78, an ER chaperone, is a key determinant of resistance to DKK3/REIC-induced apoptosis; BiP is upregulated in Ad-REIC-resistant cancer cells, and siRNA knockdown of BiP sensitizes resistant cells to apoptosis, revealing that DKK3-induced apoptosis is ER stress-dependent. Resistant clone isolation, siRNA knockdown of BiP, apoptosis assay in vitro and in vivo, western blot International journal of cancer Medium 19626590
2015 Dkk3 transgenic overexpression in mice with dilated cardiomyopathy (DCM) upregulates Dvl1 and canonical Wnt pathway proteins (cytoplasmic/nuclear beta-catenin, c-Myc, Axin2) while downregulating non-canonical Wnt pathway effectors (JNK, CAMKII, HDAC4); Dkk3 knockout has the opposite effect, indicating Dkk3 modulates cardiac Wnt signaling balance. Transgenic and knockout mouse models crossed with DCM model (cTnT-R141W), western blot, survival analysis, cardiac function assessment Laboratory investigation; a journal of technical methods and pathology High 26641069
2016 In hepatocytes, DKK3 physically binds to ASK1 under palmitate stimulation and inhibits ASK1-mediated activation of the downstream P38/JNK pathway; hepatocyte-specific DKK3 overexpression improves insulin sensitivity and reduces hepatic steatosis, while DKK3 deficiency worsens these phenotypes. Dominant-negative ASK1 blocks DKK3-deficiency effects, and constitutively active ASK1 overcomes DKK3 overexpression. Co-immunoprecipitation (DKK3-ASK1 binding), hepatocyte-specific KO and OE mouse models, dominant-negative and constitutively active ASK1, metabolic phenotyping Journal of hepatology High 27016281
2017 The Dkk3 locus encodes an intracellular isoform (Dkk3b) originating from intron 2; Dkk3b captures cytoplasmic unphosphorylated beta-catenin in an extra-nuclear complex with beta-TrCP, preventing nuclear translocation of beta-catenin and thereby arresting cell proliferation. Identification of novel transcription start site, co-immunoprecipitation of Dkk3b with beta-catenin and beta-TrCP, nuclear fractionation, cell proliferation assays, early mouse development studies PloS one Medium 28738084
2015 The cysteine-rich C-terminal core domain (C17-REIC) of DKK3/REIC is sufficient for induction of dendritic cell-like differentiation from monocytes; DKK3 induces phosphorylation of GSK-3beta and STAT proteins comparable to GM-CSF, and C17-REIC exerts anticancer immune effects in vivo. Recombinant truncated protein domain analysis, monocyte differentiation assay, GSK-3beta and STAT phosphorylation western blot, subcutaneous tumor model Oncology reports Medium 25823913
2022 DKK3 ameliorates neuropathic pain by inhibiting ASK1/JNK/p38-mediated microglial M1 polarization through the Kremen-1 and DVL-1 pathways; siRNA knockdown of Kremen-1 or DVL-1 reverses the inhibitory effects of exogenous DKK3 on ASK1/JNK/p38 activation. Intrathecal injection of recombinant DKK3, siRNA knockdown of Kremen-1 and DVL-1, western blot, immunofluorescence, ELISA, behavioral testing in SNI rats Journal of neuroinflammation Medium 35658977
2019 miR-95-3p directly targets DKK3 (validated by dual luciferase assay), and miR-95-3p-mediated suppression of DKK3 activates Wnt/beta-catenin pathway, promoting prostate cancer cell proliferation, migration, and invasion. Dual luciferase reporter assay, miRNA overexpression/inhibition, western blot for beta-catenin targets, xenograft tumor formation European review for medical and pharmacological sciences Medium 30779066
2012 In gastric cancer cells, DKK3/REIC overexpression downregulates beta-catenin, phosphorylated S6K, phosphorylated Akt, cyclin D2/E, and WAVE2, causing G1 arrest, apoptosis, and reduced migration; an anti-REIC antibody blocks these effects, confirming a cell-surface/secreted action component. Plasmid transfection, siRNA knockdown, recombinant protein treatment, anti-REIC antibody blocking, flow cytometry, western blot Cell cycle (Georgetown, Tex.) Medium 22421143

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 3054 16625202
2011 Immune signaling by RIG-I-like receptors. Immunity 1463 21616437
2020 RIG-I-like receptors: their regulation and roles in RNA sensing. Nature reviews. Immunology 1291 32203325
2007 Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. Journal of virology 840 17942531
2009 RNA recognition and signal transduction by RIG-I-like receptors. Immunological reviews 479 19120475
2008 MDA5/RIG-I and virus recognition. Current opinion in immunology 449 18272355
2015 RIG-I in RNA virus recognition. Virology 356 25749629
2018 RIG-I and Other RNA Sensors in Antiviral Immunity. Annual review of immunology 353 29677479
2015 Viral RNA detection by RIG-I-like receptors. Current opinion in immunology 349 25594890
2008 5'-Triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma. Nature medicine 328 18978796
2014 Pattern Recognition and Signaling Mechanisms of RIG-I and MDA5. Frontiers in immunology 313 25101084
2017 Crosstalk between Cytoplasmic RIG-I and STING Sensing Pathways. Trends in immunology 282 28073693
2011 Klotho suppresses RIG-I-mediated senescence-associated inflammation. Nature cell biology 227 21336305
2021 The molecular mechanism of RIG-I activation and signaling. Immunological reviews 191 34514601
2013 Master sensors of pathogenic RNA - RIG-I like receptors. Immunobiology 183 23896194
2009 RIG-I-like receptors: sensing and responding to RNA virus infection. Seminars in immunology 179 19539500
2004 Dickkopf-3/REIC functions as a suppressor gene of tumor growth. Oncogene 154 15516983
2007 Downregulation of Dkk3 activates beta-catenin/TCF-4 signaling in lung cancer. Carcinogenesis 142 18048388
2013 Intracellular pathogen detection by RIG-I-like receptors. Advances in immunology 131 23611287
2012 A structure-based model of RIG-I activation. RNA (New York, N.Y.) 121 23118418
2009 The RIG-I-like receptor LGP2 recognizes the termini of double-stranded RNA. The Journal of biological chemistry 121 19278996
2016 Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway. Cell reports 115 27425606
2001 Antiproliferative activity of REIC/Dkk-3 and its significant down-regulation in non-small-cell lung carcinomas. Biochemical and biophysical research communications 112 11708809
2002 Reduced expression of the REIC/Dkk-3 gene by promoter-hypermethylation in human tumor cells. Gene 109 11814687
2023 Exploiting RIG-I-like receptor pathway for cancer immunotherapy. Journal of hematology & oncology 107 36755342
2017 Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity. Frontiers in immunology 107 28096803
2012 MicroRNAs in the regulation of TLR and RIG-I pathways. Cellular & molecular immunology 107 23262976
2004 Decreased expression of REIC/Dkk-3 in human renal clear cell carcinoma. The Journal of urology 104 14767340
2022 DKK3 ameliorates neuropathic pain via inhibiting ASK-1/JNK/p-38-mediated microglia polarization and neuroinflammation. Journal of neuroinflammation 103 35658977
2018 A minimal RNA ligand for potent RIG-I activation in living mice. Science advances 92 29492454
2018 Regulation of RIG-I Activation by K63-Linked Polyubiquitination. Frontiers in immunology 91 29354136
2019 G3BP1 inhibits RNA virus replication by positively regulating RIG-I-mediated cellular antiviral response. Cell death & disease 87 31827077
2019 RIPLET, and not TRIM25, is required for endogenous RIG-I-dependent antiviral responses. Immunology and cell biology 84 31335993
2014 Sensing viral invasion by RIG-I like receptors. Current opinion in microbiology 84 24968321
2018 Nuclear-resident RIG-I senses viral replication inducing antiviral immunity. Nature communications 83 30097581
2023 NAD+ precursor supplementation prevents mtRNA/RIG-I-dependent inflammation during kidney injury. Nature metabolism 82 36914909
2019 NLRP12 Regulates Anti-viral RIG-I Activation via Interaction with TRIM25. Cell host & microbe 82 30902577
2014 RIG-I-like receptor LGP2 protects tumor cells from ionizing radiation. Proceedings of the National Academy of Sciences of the United States of America 80 24434553
2017 RIG-I: a multifunctional protein beyond a pattern recognition receptor. Protein & cell 79 28593618
2017 Subcellular Localizations of RIG-I, TRIM25, and MAVS Complexes. Journal of virology 78 27807226
2010 The chase for the RIG-I ligand--recent advances. Molecular therapy : the journal of the American Society of Gene Therapy 78 20461060
2015 RIG-I-like receptors and autoimmune diseases. Current opinion in immunology 76 26530735
2024 Physiological functions of RIG-I-like receptors. Immunity 74 38599168
2011 Activation of RIG-I-like receptor signal transduction. Critical reviews in biochemistry and molecular biology 72 22066529
2022 Robust delivery of RIG-I agonists using extracellular vesicles for anti-cancer immunotherapy. Journal of extracellular vesicles 70 35430766
2015 Viral pseudo-enzymes activate RIG-I via deamidation to evade cytokine production. Molecular cell 70 25752576
2022 Actin cytoskeleton remodeling primes RIG-I-like receptor activation. Cell 63 36113429
2016 DKK3 expression in hepatocytes defines susceptibility to liver steatosis and obesity. Journal of hepatology 63 27016281
2008 REIC/Dkk-3 induces cell death in human malignant glioma. Neuro-oncology 62 18443132
2011 RIG-I like receptors in antiviral immunity and therapeutic applications. Viruses 60 21994761
2009 Promoter methylation and mRNA expression of DKK-3 and WIF-1 in hepatocellular carcinoma. World journal of gastroenterology 60 19496188
2007 Triggering antiviral response by RIG-I-related RNA helicases. Biochimie 60 17379377
2019 LGP2 binds to PACT to regulate RIG-I- and MDA5-mediated antiviral responses. Science signaling 59 31575732
2007 REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer. International journal of molecular medicine 59 17273781
2009 Overexpression of REIC/Dkk-3 in normal fibroblasts suppresses tumor growth via induction of interleukin-7. The Journal of biological chemistry 58 19279003
2019 RIG-I Selectively Discriminates against 5'-Monophosphate RNA. Cell reports 51 30784585
2023 MAVS integrates glucose metabolism and RIG-I-like receptor signaling. Nature communications 50 37660168
2009 Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression. International journal of oncology 48 19212670
2007 RIG-I: tri-ing to discriminate between self and non-self RNA. Trends in immunology 47 17307033
2022 Signaling from the RNA sensor RIG-I is regulated by ufmylation. Proceedings of the National Academy of Sciences of the United States of America 46 35394863
2018 Therapeutic Targeting of RIG-I and MDA5 Might Not Lead to the Same Rome. Trends in pharmacological sciences 44 30606502
2015 Innate immunity at mucosal surfaces: the IRE1-RIDD-RIG-I pathway. Trends in immunology 44 26093676
2019 Endogenous Nucleic Acid Recognition by RIG-I-Like Receptors and cGAS. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 43 31066607
2017 RIG-I-Like Receptors and Type I Interferonopathies. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 42 28475461
2019 Know Thyself: RIG-I-Like Receptor Sensing of DNA Virus Infection. Journal of virology 41 31511389
2014 Activation and regulation of pathogen sensor RIG-I. Cytokine & growth factor reviews 41 25212896
2018 USP14 promotes K63-linked RIG-I deubiquitination and suppresses antiviral immune responses. European journal of immunology 39 30466171
2015 Dkk3 prevents familial dilated cardiomyopathy development through Wnt pathway. Laboratory investigation; a journal of technical methods and pathology 39 26641069
2013 Parts, assembly and operation of the RIG-I family of motors. Current opinion in structural biology 39 24878341
2023 RIG-I-like receptors: Molecular mechanism of activation and signaling. Advances in immunology 38 37453753
2015 Sensing viral RNAs by Dicer/RIG-I like ATPases across species. Current opinion in immunology 37 25658360
2011 Sensing of viral nucleic acids by RIG-I: from translocation to translation. European journal of cell biology 37 21496944
2022 JMJD4-demethylated RIG-I prevents hepatic steatosis and carcinogenesis. Journal of hematology & oncology 36 36333807
2019 Dual targeting of RIG-I and MAVS by MARCH5 mitochondria ubiquitin ligase in innate immunity. Cellular signalling 36 31881323
2020 RIG-I-Like Receptor LGP2 Is Required for Tumor Control by Radiotherapy. Cancer research 34 33087322
2014 An evolving arsenal: viral RNA detection by RIG-I-like receptors. Current opinion in microbiology 33 24912143
2022 A rapid RIG-I signaling relay mediates efficient antiviral response. Molecular cell 31 36521492
2018 Dickkopf homolog 3 (DKK3): A candidate for detection and treatment of cancers? Journal of cellular physiology 31 29206297
2017 RIG-I Resists Hypoxia-Induced Immunosuppression and Dedifferentiation. Cancer immunology research 29 28468914
2017 RIG-I-Like Receptor Signaling in Singleton-Merten Syndrome. Frontiers in genetics 28 28955379
2022 Friend or foe: RIG- I like receptors and diseases. Autoimmunity reviews 27 35926770
2021 The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population. Scientific reports 27 33883651
2019 MicroRNA-95-3p promoted the development of prostatic cancer via regulating DKK3 and activating Wnt/β-catenin pathway. European review for medical and pharmacological sciences 24 30779066
2017 Zyxin stabilizes RIG-I and MAVS interactions and promotes type I interferon response. Scientific reports 24 28928438
2014 Potential of adenovirus-mediated REIC/Dkk-3 gene therapy for use in the treatment of pancreatic cancer. Journal of gastroenterology and hepatology 24 24372695
2012 DNA methylation status of REIC/Dkk-3 gene in human malignancies. Journal of cancer research and clinical oncology 24 22274868
2023 The RNA polymerase III-RIG-I axis in antiviral immunity and inflammation. Trends in immunology 23 37149405
2023 The Multifaceted Role of Human Dickkopf-3 (DKK-3) in Development, Immune Modulation and Cancer. Cells 23 38201279
2017 The Dkk3 gene encodes a vital intracellular regulator of cell proliferation. PloS one 23 28738084
2016 Novel interferonopathies associated with mutations in RIG-I like receptors. Cytokine & growth factor reviews 23 26993858
2016 What Really Rigs Up RIG-I? Journal of innate immunity 23 27438016
2012 The roles of REIC gene and its encoding product in gastric carcinoma. Cell cycle (Georgetown, Tex.) 23 22421143
2022 A loosened gating mechanism of RIG-I leads to autoimmune disorders. Nucleic acids research 22 35580046
2024 Nlrp6 protects from corticosterone-induced NSPC ferroptosis by modulating RIG-1/MAVS-mediated mitophagy. Redox biology 21 38772149
2020 Small-Molecule Antagonists of the RIG-I Innate Immune Receptor. ACS chemical biology 21 31944652
2015 Are RIG-1 and MDA5 Expressions Associated with Chronic HBV Infection? Viral immunology 21 26485346
2014 Integrin antagonist augments the therapeutic effect of adenovirus-mediated REIC/Dkk-3 gene therapy for malignant glioma. Gene therapy 21 25394252
2013 Targeting TLR3 with no RIG-I/MDA5 activation is effective in immunotherapy for cancer. Expert opinion on therapeutic targets 21 23414438
2015 The cysteine-rich core domain of REIC/Dkk-3 is critical for its effect on monocyte differentiation and tumor regression. Oncology reports 20 25823913
2010 Down-regulation of BiP/GRP78 sensitizes resistant prostate cancer cells to gene-therapeutic overexpression of REIC/Dkk-3. International journal of cancer 20 19626590