Affinage

REL

Proto-oncogene c-Rel · UniProt Q04864

Length
619 aa
Mass
68.5 kDa
Annotated
2026-06-10
100 papers in source corpus 49 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

REL (c-Rel) is an NF-κB family transcription factor that binds κB DNA enhancer motifs in a sequence-specific manner and activates transcription, functioning as a master regulator of immune cell activation, proliferation, and survival (PMID:2023921, PMID:2030915). It carries a C-terminal transactivation domain restrained by an N-terminal regulatory region (PMID:2204816), and a subdomain within its Rel homology region grants it broader κB-sequence affinity than RelA/p65, accounting for its selective requirement in inducing the IL-12 subunit genes Il12a and Il12b (PMID:16166378). c-Rel acts both as a free homodimer and in heterodimers with p65/RelA, complexes held latent in the cytoplasm by IκB proteins—including a preformed cytosolic c-Rel–p65 complex masked by IκBα (PMID:8139561)—and IκBα controls c-Rel both by masking its NLS in the cytoplasm and terminating its activity in the nucleus (PMID:9488436); in naive T cells, a resting IκBβ association is exchanged for IκBα upon cytokine priming to enable rapid TCR-driven cytokine output (PMID:16226509). Nuclear entry and activity are tuned by post-translational mechanisms: ubiquitin–proteasome turnover targeting sequences C-terminal to the RHD (PMID:9857058), Peli1-mediated degradation antagonized by miR-155 (PMID:27481129), calmodulin binding that retards c-Rel-specific nuclear import (PMID:12556500), PKA-Cβ phosphorylation acting through p300/CBP (PMID:15197457), and O-GlcNAcylation at Ser350 that enhances proautoimmune cytokine expression while repressing FOXP3 (PMID:33442719). Upstream, antigen-receptor and innate signals converge selectively on c-Rel via Shc (PMID:11917142), the Bcl-10/MALT1 and CARD9–Bcl10–MALT1 modules (PMID:17660823, PMID:21283787), and caspase-8-dependent IKK activation (PMID:31147458). Functionally, c-Rel directly drives transcription of effector and proliferation programs—IL-2 through chromatin remodeling at the CD28RR (PMID:12646638), IL-21 (PMID:20639489), the cell-cycle regulators e2f3a/cyclin E and FoxM1 (PMID:14627988, PMID:20058312), and Ezh2 and Bach2 in lymphocytes (PMID:25266721, PMID:26522720)—and is essential for BCR-driven G1/S progression (PMID:12147627). It also operates as a transcriptional repressor of RelA-dependent inflammatory genes by recruiting the co-repressor HDAC1 (PMID:32062419). In disease and tissue contexts c-Rel specifies myeloid-derived suppressor cells and activated regulatory T cells that restrain anti-tumor immunity (PMID:33458695, PMID:28886380), drives fibrogenic metabolic reprogramming via Pfkfb3 (PMID:33168981), and supports neuronal survival through Bcl-xL and MnSOD induction (PMID:15818410, PMID:19094066). Inherited homozygous loss-of-function REL mutation in humans abolishes IL-12/IL-23 production and impairs T and B cell function, defining a human immunodeficiency (PMID:34623332).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1991 High

    Establishing that c-Rel is a bona fide sequence-specific κB-binding transcriptional activator distinguished it from the oncogenic, repressive v-Rel and defined its core molecular activity.

    Evidence Recombinant protein EMSA, reporter assays, and antibody supershift; biochemical identity with the inducible κB-binding protein HIVEN86A

    PMID:2023921 PMID:2030915

    Open questions at the time
    • Did not resolve which dimer partners operate at endogenous loci
    • Physiological inducers and cell contexts not defined
  2. 1990 High

    Domain mapping revealed c-Rel's modular architecture—a C-terminal transactivation domain held in check by an N-terminal regulatory region—and that its promoter is autorepressed, explaining intrinsic constraints on its activity and expression.

    Evidence GAL4 fusion deletion mapping in yeast and mammalian cells; promoter-luciferase 5' deletion and co-transfection

    PMID:2204816 PMID:2284104

    Open questions at the time
    • Mechanism of N-terminal autoinhibition not defined
    • Autorepression cofactors unknown
  3. 1991 High

    Identification of cytoplasmic ankyrin-repeat anchor proteins (pp40/IκB-like) that inhibit c-Rel DNA binding established the latency-in-cytosol model for c-Rel regulation.

    Evidence Biochemical purification, in vitro DNA-binding inhibition, immunoprecipitation and size-exclusion chromatography of a ~400 kDa complex

    PMID:1851550 PMID:1891714

    Open questions at the time
    • Identities of all ~400 kDa complex components incompletely defined
    • Stimulus-coupled release mechanism not yet shown
  4. 1994 High

    Demonstration of a preformed cytosolic c-Rel–p65 heterodimer kept latent by IκBα, more potent than p50–p65, defined the latent complex composition that signaling must liberate.

    Evidence Native protein purification, in vitro translation reconstitution, EMSA, COS7 co-expression reporter assays

    PMID:8139561

    Open questions at the time
    • In vivo stoichiometry of c-Rel dimer pools unclear
    • Selectivity determinants among partners not addressed
  5. 1998 High

    Dissecting IκBα's bipartite control and the ubiquitin–proteasome turnover of c-Rel established how its nuclear access and lifetime are gated; PPX/PP4 was identified as a positive regulator of DNA binding.

    Evidence IκBα domain mapping with subcellular fractionation; cell-free degradation and ubiquitination assays with deletion mutants; PPX co-IP and catalytic-mutant reporter assays

    PMID:9488436 PMID:9837938 PMID:9857058

    Open questions at the time
    • The E3 ligase mediating c-Rel turnover not identified here
    • Phosphosites targeted by PPX unknown
  6. 1995 Medium

    Linking c-Rel to antigen-receptor signaling via calcineurin defined it as an inducible component of TCR/BCR-driven κB complexes, connecting it to lymphocyte activation.

    Evidence EMSA, IL-2Rα promoter reporter, FK506 inhibition and calcineurin co-expression in B and T cells

    PMID:7532676

    Open questions at the time
    • Direct calcineurin substrate within the pathway not defined
    • Single lab, pharmacological inference
  7. 2002 Medium

    Genetic and epistasis studies placed Shc upstream of c-Rel in TCR signaling and showed c-Rel is required to remodel chromatin and drive the IL-2 gene, establishing its role in T cell effector transcription.

    Evidence Shc-deficient Jurkat rescue with c-Rel-ER; c-Rel knockout mice with restriction-enzyme accessibility assays at the IL-2 CD28RR

    PMID:11917142 PMID:12646638

    Open questions at the time
    • Intervening signaling steps between Shc and c-Rel undefined
    • Chromatin remodeling machinery recruited by c-Rel not identified
  8. 2002 High

    c-Rel knockout studies established its essential role in BCR-driven G1/S progression by controlling cyclin D3, cyclin E, CDK activity and Rb phosphorylation, linking c-Rel to lymphocyte proliferation.

    Evidence c-Rel knockout B cells, cell-cycle flow cytometry, cyclin/CDK/pRb/E2F immunoblots and kinase assays

    PMID:12147627

    Open questions at the time
    • Direct vs indirect control of each cyclin not resolved here
    • Did not establish which target gene is rate-limiting
  9. 2003 Medium

    Identifying e2f3a as a direct c-Rel target and showing cyclin E plus Bcl-xL rescues proliferation defined the transcriptional route by which c-Rel feeds the CDK/Rb/E2F axis.

    Evidence e2f3a promoter reporter, bcl-xL transgenic rescue, cyclin E protein transduction in c-Rel-deficient B cells

    PMID:14627988

    Open questions at the time
    • Direct promoter occupancy by ChIP not shown in this study
    • Single lab
  10. 2003 High

    Demonstrating that calmodulin binds c-Rel near its NLS and selectively retards its nuclear import (but not RelA's) revealed a calcium-coupled, subunit-specific brake on c-Rel activation.

    Evidence Co-IP, CaM-binding mutant analysis, nuclear fractionation, IL-2/GM-CSF reporter assays

    PMID:12556500

    Open questions at the time
    • Quantitative contribution to import kinetics in primary cells unclear
    • Upstream Ca2+ signal coupling not mapped
  11. 2001 High

    Showing PU.1/Spi-B directly drive c-rel transcription and that Rel reintroduction rescues B cells established the transcriptional control of c-Rel expression and its requirement for B cell homeostasis.

    Evidence c-rel promoter mapping, EMSA, bone marrow reconstitution and rescue

    PMID:11672537

    Open questions at the time
    • Other transcriptional inputs to c-rel not exhaustively defined
    • Whether Ets control is dynamic during activation unknown
  12. 2001 High

    Cell-type-resolved knockout/ChIP studies showed c-Rel selectively controls IL-12p40 in macrophages and IL-12p35 in CD8+ dendritic cells, revealing context-specific target selectivity beyond DNA-binding affinity.

    Evidence c-Rel knockout mice, EMSA/supershift, ChIP, RT-PCR and ELISA across macrophages and DCs

    PMID:11058167 PMID:11602633

    Open questions at the time
    • Cofactors imposing cell-type selectivity not identified here
    • Chromatin context determinants unresolved
  13. 2005 High

    A chimeric domain-swap mapped c-Rel's broad κB-sequence affinity to a 46-residue RHR subdomain and showed this intrinsic DNA-binding property—not selective coactivators—explains the c-Rel requirement at Il12a/Il12b.

    Evidence c-Rel/p65 chimeras, quantitative EMSA across κB panels, macrophage/DC knockout validation, coactivator interaction studies

    PMID:16166378

    Open questions at the time
    • Structural basis for the affinity difference not solved here
    • Generalizability to all c-Rel-selective genes untested
  14. 2005 High

    Defining a resting IκBβ-to-IκBα exchange in naive T cells upon cytokine priming explained how prior inflammatory exposure accelerates c-Rel-dependent effector cytokine output.

    Evidence c-Rel knockout mice, differential IκBα vs IκBβ co-IP, cytokine priming assays in naive vs effector T cells

    PMID:16226509

    Open questions at the time
    • Mechanism driving the IκB exchange not defined
    • Why effector T cells lack this circuit unexplained
  15. 2007 High

    Genetic dissection of the BCR pathway showed MALT1 selectively activates c-Rel (not RelA) downstream of Bcl-10/IKK, establishing a dedicated c-Rel survival subprogram.

    Evidence Bcl-10- and MALT1-deficient B cells, IKK assays, subunit-specific translocation and gene expression analysis

    PMID:17660823

    Open questions at the time
    • Molecular basis of MALT1's subunit selectivity unresolved
    • Survival gene set incompletely catalogued
  16. 2004 Medium

    PKA-Cβ was shown to bind and directly phosphorylate c-Rel and enhance its transcription via p300/CBP, identifying a phosphorylation input that boosts c-Rel transactivation.

    Evidence Co-IP, in vitro kinase assay, EMSA, reporter assays

    PMID:15197457

    Open questions at the time
    • Phosphoacceptor residue(s) not mapped
    • In vivo relevance not established
  17. 2010 High

    ChIP/EMSA and knockout studies defined direct c-Rel targets governing humoral and proliferative programs—IL-21 (Th17/Tfh/germinal center), FoxM1 (hepatocyte proliferation)—broadening c-Rel's transcriptional repertoire beyond lymphoid cytokines.

    Evidence c-Rel knockout mice, EMSA, ChIP, promoter reporters, IL-21 rescue; partial hepatectomy and CCl4 injury models

    PMID:20058312 PMID:20639489

    Open questions at the time
    • Combinatorial cofactors at these promoters undefined
    • Tissue specificity determinants unclear
  18. 2011 High

    Innate C-type lectin signaling (Dectin-1/2) was shown to converge on c-Rel via CARD9–Bcl10–MALT1 to drive Th17-polarizing cytokines, extending the dedicated c-Rel module to antifungal innate immunity.

    Evidence MALT1 inhibition, siRNA, subunit-specific reporters and cytokine ELISA in human DCs

    PMID:21283787

    Open questions at the time
    • How dectin-2 achieves exclusive c-Rel activation not resolved
    • Direct target promoters not mapped here
  19. 2011 Medium

    Co-IP domain mapping identified Foxp3 as a c-Rel interactor and cardiac ChIP identified MEF/Gata4/Tbx targets, extending c-Rel's interaction and target landscape into Treg biology and cardiac hypertrophy.

    Evidence Foxp3 co-IP with deletion mutants; c-Rel knockout mice, angiotensin model, ChIP for cardiac targets

    PMID:21490927 PMID:22210479

    Open questions at the time
    • Functional consequence of Foxp3–c-Rel binding not tested in same study
    • Cardiac target regulation single lab
  20. 2014 High

    ChIP-based identification of Ezh2 (first intron) and Bach2 as direct c-Rel targets linked c-Rel to epigenetic and tumor-suppressor programs in normal and malignant lymphocytes.

    Evidence ChIP and ChIP-seq, c-Rel knockout and siRNA knockdown, RT-PCR/immunoblot in B and T cells and lymphoma lines

    PMID:25266721 PMID:26522720

    Open questions at the time
    • How c-Rel coordinates these opposing tumor programs unclear
    • Bach2 study relied on published ChIP-seq reanalysis
  21. 2019 High

    Caspase-8 enzymatic activity was placed upstream of c-Rel by showing it is required for IKK phosphorylation/c-Rel nuclear translocation and that c-Rel overexpression rescues TLR-induced cytokines, adding a death-protease branch to c-Rel activation.

    Evidence Caspase-8-deficient macrophages, IKK phosphorylation assay, nuclear fractionation, c-Rel overexpression rescue

    PMID:31147458

    Open questions at the time
    • Direct caspase-8 substrate in the pathway undefined
    • Selectivity for c-Rel vs other subunits not fully resolved
  22. 2020 High

    Discovery that c-Rel recruits HDAC1 to competitively occupy and repress RelA-dependent inflammatory promoters established a dual activator/repressor role, with a Y25H DNA-binding mutant abolishing repression.

    Evidence Genetic deletion, c-Rel–HDAC1 co-IP, ChIP, reporter assays, Y25H mutagenesis

    PMID:32062419

    Open questions at the time
    • Genome-wide scope of repressed targets not mapped
    • Switch between activator and repressor modes undefined
  23. 2020 High

    Cell-type-specific knockouts established c-Rel as a driver of pathogenic programs—MDSC specification via an enhanceosome, fibrogenic metabolic reprogramming through Pfkfb3, and neuronal survival—nominating it as a therapeutic target.

    Evidence Myeloid- and hepatocyte/macrophage-specific c-Rel knockouts, tumor and fibrosis models, pharmacological inhibition; neuronal MPTP/MPP+ models with IT901

    PMID:15818410 PMID:19094066 PMID:31986466 PMID:33168981 PMID:33458695

    Open questions at the time
    • Direct enhanceosome composition incompletely defined
    • Pfkfb3 regulation as direct vs indirect target not fully resolved
  24. 2021 High

    Defining inherited human REL deficiency demonstrated c-Rel's non-redundant role in human immunity, with loss abolishing IL-12/IL-23 production and impairing T and B cell function.

    Evidence Patient cells with homozygous REL LOF mutation, cytokine ELISA, flow cytometry, B cell differentiation and gene expression analyses

    PMID:34623332

    Open questions at the time
    • Genotype–phenotype spectrum across patients incomplete
    • Therapeutic correction not addressed
  25. 2021 High

    Identifying O-GlcNAcylation at Ser350 and METTL3-dependent m6A control of REL mRNA revealed metabolic and epitranscriptomic layers that bias c-Rel between FOXP3 repression, proautoimmune cytokine output, and tumor-promoting NF-κB activity.

    Evidence S350A mutagenesis, ChIP, autoimmune diabetes models, O-GlcNAc chemical modulation; meRIP-seq, YTHDF2 co-knockdown, tumor models

    PMID:33442719 PMID:33484966

    Open questions at the time
    • Enzymes adding/removing O-GlcNAc at Ser350 in vivo not pinned down
    • m6A regulation single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How c-Rel's modifications, dimer composition, and cofactor recruitment are integrated to select between gene-activating, gene-repressing, pro- and anti-tumoral, and pro-survival outputs in a given cell remains unresolved.
  • No unified model linking PTM state to target gene choice
  • Structural basis of dimer- and context-selective DNA occupancy unsolved
  • Functional role of several interactors (e.g. galectin-16) untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 4
Pathway
R-HSA-168256 Immune System 6 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 5 R-HSA-1640170 Cell Cycle 4
Partners
CALM1FOXP3HDAC1MALT1NFKB1NFKBIAPRKACBRELA
Complex memberships
c-Rel–IκBα latent cytoplasmic complexc-Rel–p65 (RelA) NF-κB heterodimerp50–c-Rel NF-κB heterodimer

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 The Rel-associated protein pp40 (IκB-like) inhibits DNA binding activity of p50:c-Rel heteromers and c-Rel homodimers, suggesting c-Rel is held in the cytosol by interaction with cytoplasmic anchor molecules containing ankyrin repeats. Biochemical purification and in vitro DNA binding inhibition assay Science High 1891714
1991 c-Rel protein binds κB DNA sites in a sequence-specific manner and activates transcription from κB-containing promoters; v-Rel, by contrast, suppresses this transcription, acting as a dominant negative. Bacterial expression, EMSA, transient transfection reporter assay, anti-rel antibody supershift Proceedings of the National Academy of Sciences of the United States of America High 2023921
1990 Mouse c-Rel protein has a C-terminal transcriptional transactivation domain (residues 403–568) and an N-terminal regulatory domain that suppresses transactivation; deletion of the N-terminal half augments transactivation function. GAL4 fusion domain mapping, transient transfection reporter assay in yeast and mammalian cells Molecular and cellular biology High 2204816
1992 I-Rel (a novel 66 kDa Rel-related protein, alias of REL locus product) forms heterodimers with p50 and inhibits its DNA-binding activity through an N-terminal inhibitory domain, but does not associate with p65; I-Rel suppresses NF-κB-induced transcription and its expression is induced by mitogenic stimulation. cDNA cloning, co-immunoprecipitation, EMSA, transient transfection reporter assay, Northern blot Genes & development High 1577270
1991 c-Rel protein exists in a high molecular weight (~400 kDa) cytoplasmic complex with other cellular proteins (including proteins of ~36 kDa, ~115 kDa, ~124 kDa) in both avian and murine cells; complex formation is not dependent on v-Rel. Immunoprecipitation, size-exclusion chromatography (Sephacryl S-400) Oncogene Medium 1851550
1994 c-Rel forms a preformed heterodimeric complex with p65 (RelA) in the cytosol that is kept latent by IκBα association; upon stimulation this c-Rel–p65 complex translocates to the nucleus and is a potent transcriptional activator of κB-containing promoters, more active than p50–p65. Protein purification from HeLa cytosol, in vitro translation reconstitution, EMSA, co-expression in COS7 cells, transient transfection reporter assay, detergent activation assay Molecular and cellular biology High 8139561
1990 The c-rel promoter is autoregulated: co-expression of c-Rel protein decreases expression from its own minimal promoter, demonstrating transcriptional autorepression. Promoter-luciferase reporter assay, 5′ deletion analysis, co-transfection Oncogene Medium 2284104
1995 c-Rel is a component of antigen receptor-induced κB-binding complexes in B and T cells; its induction requires both phorbol ester and ionomycin (dual signal) and is blocked by FK506 (calcineurin inhibitor); calcineurin co-expression augments c-Rel-dependent transactivation of the IL-2Rα promoter, indicating a calcineurin-dependent pathway for c-Rel activation. EMSA, transient transfection reporter assay, pharmacological inhibition (FK506), calcineurin co-expression The Journal of experimental medicine Medium 7532676
1998 Protein phosphatase X (PPX/PP4) specifically associates with c-Rel, p50, and RelA; overexpression of catalytically active PPX (but not inactive mutants) stimulates c-Rel DNA-binding activity and NF-κB-mediated transcription, identifying PPX as a positive regulator of c-Rel. Co-immunoprecipitation, EMSA, transient transfection reporter assay, catalytic mutant analysis The Journal of biological chemistry Medium 9837938
1998 c-Rel protein turnover is regulated by the ubiquitin–proteasome pathway; ubiquitinated c-Rel conjugates accumulate with proteasome inhibitors; a region between residues 118–171 (immediately C-terminal to the Rel homology domain) is important for ubiquitin conjugation, while C-terminal sequences mediate susceptibility to degradation. Cell-free in vitro degradation assay, proteasome inhibitor treatment, immunoprecipitation, deletion mutant analysis The Journal of biological chemistry High 9857058
1998 IκBα regulates c-Rel in two distinct subcellular compartments via discrete domains: the N-terminal and central ankyrin regions retain c-Rel in the cytoplasm by masking its NLS, while the central ankyrin domain plus a C-terminal PEST-proximal acidic region terminate c-Rel transcriptional activity in the nucleus. Domain deletion/mapping of IκBα, subcellular fractionation, transcriptional reporter assay Molecular and cellular biology High 9488436
2000 c-Rel is selectively required for IL-12 p40 gene induction in LPS-activated macrophages; p50/p65 and p50/c-Rel heterodimers bind the IL-12 p40 Rel site with comparable affinity and transactivation in vitro, yet only c-Rel deficiency dramatically reduces p40 mRNA and protein in vivo, indicating selectivity is not explained by DNA binding affinity alone. c-Rel knockout mice, EMSA, qRT-PCR, ELISA, transient transfection Proceedings of the National Academy of Sciences of the United States of America High 11058167
2001 In CD8+ dendritic cells, c-Rel complexes bind directly to the IL-12 p35 promoter and are required for induced p35 transcription by microbial stimuli; this is distinct from macrophages where c-Rel controls p40, demonstrating cell-type-specific regulation of IL-12 subunits by c-Rel. c-Rel knockout mice, EMSA with supershift, chromatin immunoprecipitation (ChIP), RT-PCR, ELISA The Journal of experimental medicine High 11602633
2001 PU.1 and Spi-B Ets transcription factors directly regulate c-rel transcription through three PU.1/Spi-B binding sites in the murine c-rel promoter; loss of both Ets factors dramatically reduces c-Rel expression in splenic B cells, and Rel protein reintroduction rescues B cell numbers. Promoter analysis, EMSA, bone marrow reconstitution, rescue experiment Immunity High 11672537
2002 c-Rel is required for TCR/CD28-induced chromatin remodeling across the IL-2 gene promoter in primary CD4+ T cells; c-Rel deficiency abolishes global chromatin accessibility changes and also specifically impairs accessibility at the c-Rel binding site in the CD28RR region, paralleling loss of IL-2 mRNA and protein. c-Rel knockout mice, restriction enzyme accessibility assay (REAA), RT-PCR, ELISA Journal of immunology High 12646638
2002 c-Rel is essential for BCR-mediated B cell proliferation and G1/S cell cycle progression; c-Rel-deficient B cells fail to induce cyclin D3 and cyclin E, have reduced CDK activity, incomplete pRb phosphorylation, and poor E2F expression upon BCR stimulation. c-Rel knockout mice, flow cytometry cell cycle analysis, immunoblot for cyclins/CDKs/pRb/E2F, kinase assays International immunology High 12147627
1997 Expression of c-Rel in HeLa cells causes G1/S growth arrest correlated with nuclear localization of c-Rel; arrest is accompanied by decreased E2F DNA binding, accumulation of hypophosphorylated Rb, reduced Cdk2 kinase activity, elevated p21WAF1 and p53 protein stability; deletion of c-Rel C-terminal transactivation domains abolishes these effects. Tetracycline-inducible expression system, in vitro Cdk2 kinase assay, EMSA, immunoblot, pulse-chase analysis, flow cytometry Molecular and cellular biology High 9343416
2003 c-Rel directly regulates e2f3a promoter/enhancer transcription and thereby controls cyclin E expression and cell cycle progression in B lymphocytes; Bcl-xL alone cannot rescue proliferation of c-Rel-deficient B cells, but cyclin E cooperates with Bcl-xL to restore cell cycle entry via the CDK/Rb/E2F pathway. bcl-xL transgenic rescue, cyclin E protein transduction, c-Rel-deficient B cells, reporter assay for e2f3a promoter Oncogene Medium 14627988
2003 Ca2+/calmodulin (CaM) directly interacts with c-Rel and RelA near their nuclear localization signals after IκB release; CaM binding-deficient c-Rel mutants show increased nuclear accumulation and transcriptional activity on IL-2 and GM-CSF promoters, demonstrating CaM inhibits nuclear import of c-Rel specifically (but not RelA) following stimulation. Co-immunoprecipitation, CaM-binding mutant analysis, nuclear fractionation, transcriptional reporter assay Molecular and cellular biology High 12556500
2005 A 46-residue subdomain within the 86-residue segment of c-Rel's Rel homology region (RHR) confers enhanced DNA-binding affinity to a broader range of κB sequences compared with p65, and this property—not c-Rel-specific coactivator interactions—accounts for the c-Rel-selective requirement for Il12b and Il12a gene induction. c-Rel/p65 chimeric protein analysis, EMSA with broad panel of κB sequences, macrophage/DC knockout assays, coactivator interaction studies Genes & development High 16166378
2004 PKA catalytic subunit beta (PKA-Cβ) physically interacts with c-Rel, directly phosphorylates it in vitro, and stimulates its transcriptional activity; coactivators p300/CBP are at least partially responsible for the enhanced activation by the c-Rel–PKA-Cβ axis. Co-immunoprecipitation, immunoprecipitation-in vitro kinase phosphorylation assay, EMSA, transcriptional reporter assay Journal of molecular medicine Medium 15197457
2005 Neuroprotection by mGlu5 receptor agonists against amyloid-β toxicity depends on c-Rel activation; c-Rel induces MnSOD and Bcl-XL expression; RNAi knockdown of c-Rel suppresses both antiapoptotic genes and abolishes neuroprotection, while c-Rel overexpression rescues neurons from Aβ toxicity. RNA interference, c-Rel overexpression, immunoblot, neuronal viability assay in primary cortical neurons Cell death and differentiation Medium 15818410
2007 MALT1 selectively activates c-Rel (but not RelA) downstream of B cell receptor signaling; Bcl-10 is required for IKK recruitment and activation of both RelA and c-Rel, while MALT1 participates only in the c-Rel subprogram controlling a distinct survival gene subset. Bcl-10- and MALT1-deficient B cells, IKK activity assays, NF-κB subunit-specific nuclear translocation assays, gene expression analysis Nature immunology High 17660823
2007 Nuclear CD40 physically interacts with c-Rel (but not p65) in large B-cell lymphoma cells; nuclear CD40–c-Rel complexes bind promoters of NF-κB target genes (CD154, BLyS/BAFF, Bfl-1/A1); wild-type but not NLS-mutated CD40 enhances c-Rel-mediated BLyS promoter activation and LBCL proliferation. Co-immunoprecipitation, ChIP, promoter reporter assay, NLS mutation analysis, proliferation assay Blood Medium 17567982
2009 In neurons, c-Rel-containing dimers (p50/c-Rel and RelA/c-Rel) but not p50/RelA promote Bcl-xL transcription, conferring neuroprotection; during ischemia, p50/RelA activation is associated with inhibition of c-Rel/RelA dimer, increased Bim/Noxa expression and enhanced neuronal vulnerability. Oxygen-glucose deprivation (OGD) model, mouse ischemia model, targeted RNAi knockdown of subunits, NF-κB subunit-specific EMSA, Bcl-xL and Bim promoter assays, immunoblot Journal of neurochemistry Medium 19094066
2011 Dectin-1 and dectin-2 C-type lectins activate c-Rel selectively via the CARD9-Bcl10-MALT1 signaling module in human dendritic cells; MALT1 inhibition abrogates c-Rel activation and Th17-polarizing cytokine (IL-1β, IL-23p19) expression; dectin-2 selectively activates c-Rel without activating other NF-κB subunits. MALT1 inhibition, siRNA knockdown, NF-κB subunit-specific reporter assays, cytokine ELISA, human DC stimulation PLoS pathogens High 21283787
2011 Foxp3 directly or as part of a multimeric complex engages c-Rel; the N-terminal region of Foxp3 is required for c-Rel binding but not NFAT binding, while forkhead domain deletion abolishes NFAT but not c-Rel interaction, identifying distinct interaction domains. Co-immunoprecipitation, deletion mutant analysis PloS one Medium 21490927
2010 c-Rel is required for IL-21 gene expression in T lymphocytes; a c-Rel binding site in the proximal IL-21 promoter is confirmed to bind c-Rel in vitro and in vivo, regulating IL-21 transcription; downstream, c-Rel deficiency impairs Th17, Tfh, and germinal center B cell development. c-Rel knockout mice, EMSA, ChIP, RT-PCR, ELISA, promoter reporter assay, IL-21 rescue experiment Journal of immunology High 20639489
2010 c-Rel binds the FoxM1 promoter in the regenerating liver (shown by ChIP), is required for FoxM1 induction and downstream targets cyclin B1 and Cdc25C, and regulates hepatocyte proliferation; c-Rel deficiency impairs both the inflammatory (RANTES/CCL5 induction) and fibrogenic wound-healing responses to liver injury. c-Rel knockout mice, ChIP, RT-PCR, immunoblot, partial hepatectomy and CCl4 injury models Hepatology High 20058312
2016 miR-155 represses Peli1, a ubiquitin ligase that promotes c-Rel degradation; this miR-155–Peli1–c-Rel axis controls c-Rel protein levels, cellular proliferation, and CD40L expression in T follicular helper cells. miR-155- and Peli1-deficient mice, immunoblot for c-Rel protein, flow cytometry, functional T cell assays The Journal of experimental medicine Medium 27481129
2014 c-Rel is a component of the TRAIL-inducible NF-κB complex in pancreatic cancer cells; siRNA knockdown of c-Rel sensitizes TRAIL-resistant PDAC cells to apoptosis; c-Rel drives expression of NFATc2 which in turn induces COX-2, constituting a c-Rel–NFATc2–COX-2 antiapoptotic pathway. siRNA knockdown, gel-shift (EMSA), gene expression array, co-transfection, pharmacological COX-2 inhibition Cell death & disease Medium 25299780
2014 c-Rel directly activates Ezh2 transcription in lymphoid cells by binding to the first intron of the Ezh2 locus; c-Rel deficiency abolishes Ezh2 upregulation in activated B and T cells, and c-Rel knockdown in malignant cells reduces Ezh2 expression and sensitizes cells to Ezh2 inhibition. ChIP, c-Rel knockout mice, c-Rel-deficient lymphocytes, siRNA knockdown, RT-PCR, immunoblot The Journal of biological chemistry High 25266721
2015 c-Rel regulates Bach2 (B-cell tumour suppressor) expression; ChIP-seq data confirm Bach2 as a c-Rel target gene in transformed human B cells; loss of c-Rel or IKK pathway inhibition reduces Bach2 expression in Burkitt lymphoma cells. ChIP-seq (published data analysis), RT-PCR, immunoblot, c-Rel knockout mice, IKK/NF-κB inhibitor treatment Oncogene Medium 26522720
2011 c-Rel stimulates cardiac hypertrophy and fibrosis; c-Rel-deficient mice have smaller hearts and are protected from angiotensin-induced hypertrophy; ChIP identified myocyte enhancer factor (MEF), Gata4, and Tbx proteins as c-Rel transcriptional targets in the heart; p50 overexpression represses c-Rel levels and hypertrophic response. c-Rel knockout mice, angiotensin infusion model, ChIP, gene expression analysis, p50 overexpression in H9c2 cells, immunohistochemistry The American journal of pathology Medium 22210479
2020 c-Rel functions as a transcriptional repressor of RelA-dependent inflammatory genes by selectively binding the co-repressor HDAC1 and competitively occupying promoters of inflammatory genes; a point mutation at tyrosine 25 (Y25H) in c-Rel's DNA-binding domain abolishes DNA binding and repressive function. Genetic deletion, co-immunoprecipitation (c-Rel–HDAC1), ChIP, promoter reporter assay, site-directed mutagenesis (Y25H) iScience High 32062419
2020 c-Rel specifies generation of myeloid-derived suppressor cells (MDSCs) by selectively activating pro-tumoral genes while repressing anti-tumoral genes through a c-Rel enhanceosome; myeloid-specific c-Rel deficiency markedly inhibits cancer growth in mice. Myeloid-specific c-Rel knockout mice, gene expression analysis, pharmaceutical c-Rel inhibition, tumor growth assays Nature cancer Medium 33458695
2020 c-Rel controls metabolic reprogramming required for fibrogenic activities of hepatocytes and macrophages through Pfkfb3 as a key downstream metabolic mediator; cell-type-specific deletion of c-Rel in hepatocytes or macrophages independently suppresses liver fibrosis with additive effects when combined; pharmacological c-Rel inhibition attenuates multi-organ fibrosis. Cell-type-specific c-Rel knockout mice (hepatocyte- and macrophage-specific), carbon tetrachloride fibrosis model, gene expression analysis, pharmacological inhibition Nature metabolism High 33168981
2021 c-Rel O-GlcNAcylation at serine 350 negatively regulates FOXP3 expression: hyperglycemia-induced O-GlcNAcylation decreases c-Rel binding at the FOXP3 promoter; S350A mutation augments TCR-induced FOXP3 expression and resists O-GlcNAc-dependent repression. This contrasts with c-Rel O-GlcNAcylation enhancing proautoimmune cytokine (IL-2, IFN-γ, GM-CSF) expression. Site-directed mutagenesis (S350A), ChIP, mouse models of autoimmune diabetes, O-GlcNAc inhibitor/enhancer treatment, immunoblot Glycobiology High 33442719
2021 Inherited human c-Rel deficiency (loss-of-function mutation in REL) abolishes IL-12 and IL-23 production by cDC1s and monocytes, impairs CD86 induction on cDCs, reduces IL-2 production by naive T cells (at later phases), impairs memory CD4+ T cell cytokine production, and blocks MYC and BCL2L1 induction in naive B cells, compromising B cell survival/proliferation and Ig secretion. Patient-derived cells with homozygous REL LOF mutation, cytokine ELISA, flow cytometry, B cell differentiation assays, gene expression analysis The Journal of clinical investigation High 34623332
2019 Caspase-8 enzymatic activity is required for optimal IκB kinase phosphorylation and nuclear translocation of c-Rel; overexpression of c-Rel restores IL-12 and IL-1β expression in caspase-8-deficient macrophages, placing caspase-8 upstream of c-Rel in the TLR-induced inflammatory gene expression pathway. Caspase-8-deficient macrophages, IKK phosphorylation assay, nuclear fractionation, c-Rel overexpression rescue, cytokine ELISA Proceedings of the National Academy of Sciences of the United States of America High 31147458
2002 Shc adapter protein is required for TCR-induced c-Rel nuclear translocation and IL-2 production; in Shc-deficient Jurkat cells, c-Rel activation is impaired; restoration of c-Rel activity using an ER-fusion protein rescues IL-2 promoter activation, placing Shc upstream of c-Rel in TCR signaling. Shc-deficient Jurkat mutant cells, EMSA for c-Rel nuclear translocation, inducible c-Rel-ER fusion rescue, IL-2 promoter reporter assay Proceedings of the National Academy of Sciences of the United States of America Medium 11917142
2005 In naive T cells, c-Rel is associated primarily with IκBβ (not IκBα) in the resting state; priming by TNF-α and IL-1β shifts c-Rel to IκBα-associated complexes that are readily targeted by TCR signals, enabling faster and higher IL-2 and IFN-γ production; this mechanism is c-Rel-dependent and does not operate in effector T cells. c-Rel knockout mice, co-immunoprecipitation of c-Rel with IκBα vs IκBβ, cytokine RT-PCR and ELISA, cytokine priming assay in naive vs effector T cells Immunity High 16226509
2004 NEMO mutations in XHM-ED patients impair CD40-mediated activation of both p65 and c-Rel in B cells; IL-4 can enhance p65 but not c-Rel activity, demonstrating that c-Rel and p65 have different activation requirements downstream of NEMO; c-Rel deficiency correlates with absent Ig somatic hypermutation and defective class switch recombination despite normal AID expression. Patient B cells with hypomorphic NEMO mutations, NF-κB subunit-specific nuclear translocation assays, microarray, functional B cell differentiation assays The Journal of clinical investigation Medium 15578091
2020 c-Rel activation in dopaminergic neurons maintains neuronal survival by initiating anti-apoptotic gene expression; c-Rel inhibits microglial overactivation by suppressing inflammatory gene expression; pharmacological inhibition of c-Rel (IT901) aggravates MPTP-induced dopaminergic neuron damage and promotes microglial activation in vivo. MPP+-treated SH-SY5Y cells, LPS-challenged BV2 microglial cells, MPTP mouse model, c-Rel inhibitor IT901, immunoblot, immunostaining Redox biology Medium 31986466
1991 The protein product of the human c-rel proto-oncogene is structurally identical to HIVEN86A, an inducible κB-binding protein; human c-Rel/HIVEN86A binds κB enhancer motifs in HIV, immunoglobulin κ, MHC class I, and IL-2R genes. Protein sequencing and peptide mapping, EMSA with defined binding sites Oncogene Medium 2030915
2017 NF-κB c-Rel ablation specifically impairs generation of activated Tregs (aTregs) but not other Treg subsets; melanoma growth is reduced only in mice lacking c-Rel (not p65) in Tregs; chemical inhibition of c-Rel delays melanoma growth and potentiates anti-PD-1 therapy via aTreg-mediated immunosuppression. Conditional c-Rel and p65 knockout mice in Tregs, melanoma tumor models, anti-PD-1 combination therapy, flow cytometry Cell High 28886380
2021 METTL3-mediated m6A modification targets c-Rel and RelA mRNAs; disruption of METTL3 leads to increased c-Rel and RelA expression via reduced YTHDF2-dependent mRNA decay, activating NF-κB and promoting IL-8 secretion that recruits tumor-associated neutrophils. meRIP-seq, RNA-seq, gain/loss-of-function studies, YTHDF2 co-knockdown, IL-8 functional assays, mouse tumor models Molecular therapy Medium 33484966
2020 NF-κB c-Rel subunit c-Rel promotes phagocytosis and cytokine secretion in splenic macrophages; p65/c-Rel dimers are activated in hypersplenic macrophages as shown by co-immunoprecipitation; siRNA-mediated silencing of c-Rel blocks phagocytosis, secretion, and expression of IL-1α, IL-1β, IFN-γ, TGF-β1, and TNF-α. Co-immunoprecipitation, ChIP, siRNA knockdown, κB/luciferase reporter, phagocytosis assays The international journal of biochemistry & cell biology Medium 23195252
2020 Human galectin-16 (Gal-16) localizes predominantly to the nucleus and physically interacts with c-Rel as shown by pull-down and microscale thermophoresis; this interaction suggests Gal-16 may regulate NF-κB/c-Rel-dependent signaling in lymphocytes. X-ray crystallography of Gal-16, co-immunoprecipitation pull-down, microscale thermophoresis, EGFP-tagging and cellular localization imaging Biochimica et biophysica acta. General subjects Low 33011338

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Aberrant rel/nfkb genes and activity in human cancer. Oncogene 949 10602468
2017 NF-κB c-Rel Is Crucial for the Regulatory T Cell Immune Checkpoint in Cancer. Cell 259 28886380
1991 Rel-associated pp40: an inhibitor of the rel family of transcription factors. Science (New York, N.Y.) 250 1891714
2000 Selective requirement for c-Rel during IL-12 P40 gene induction in macrophages. Proceedings of the National Academy of Sciences of the United States of America 241 11058167
2002 Critical roles of c-Rel in autoimmune inflammation and helper T cell differentiation. The Journal of clinical investigation 182 12235116
1991 c-rel activates but v-rel suppresses transcription from kappa B sites. Proceedings of the National Academy of Sciences of the United States of America 164 2023921
1990 The mouse c-rel protein has an N-terminal regulatory domain and a C-terminal transcriptional transactivation domain. Molecular and cellular biology 161 2204816
2003 Mitogenic and antiapoptotic role of constitutive NF-kappaB/Rel activity in pancreatic cancer. International journal of cancer 155 12767057
2021 METTL3 restrains papillary thyroid cancer progression via m6A/c-Rel/IL-8-mediated neutrophil infiltration. Molecular therapy : the journal of the American Society of Gene Therapy 153 33484966
1992 I-Rel: a novel rel-related protein that inhibits NF-kappa B transcriptional activity. Genes & development 153 1577270
2001 c-Rel regulates interleukin 12 p70 expression in CD8(+) dendritic cells by specifically inducing p35 gene transcription. The Journal of experimental medicine 147 11602633
1992 The inhibitory ankyrin and activator Rel proteins. Current opinion in genetics & development 147 1386268
2011 Selective C-Rel activation via Malt1 controls anti-fungal T(H)-17 immunity by dectin-1 and dectin-2. PLoS pathogens 132 21283787
2011 The c-Rel Transcription Factor in Development and Disease. Genes & cancer 124 22207895
2004 The c-Rel transcription factor and B-cell proliferation: a deal with the devil. Oncogene 119 14755244
1999 NF-kappa B/Rel transcription factors: c-Rel promotes airway hyperresponsiveness and allergic pulmonary inflammation. Journal of immunology (Baltimore, Md. : 1950) 110 10586083
2005 A c-Rel subdomain responsible for enhanced DNA-binding affinity and selective gene activation. Genes & development 109 16166378
1998 c-Rel is essential for B lymphocyte survival and cell cycle progression. European journal of immunology 107 9862367
2009 Differential role for c-Rel and C/EBPbeta/delta in TLR-mediated induction of proinflammatory cytokines. Journal of immunology (Baltimore, Md. : 1950) 99 19454718
2003 c-Rel is required for chromatin remodeling across the IL-2 gene promoter. Journal of immunology (Baltimore, Md. : 1950) 97 12646638
1997 c-Rel arrests the proliferation of HeLa cells and affects critical regulators of the G1/S-phase transition. Molecular and cellular biology 94 9343416
2006 Role for IkappaBalpha, but not c-Rel, in skeletal muscle atrophy. American journal of physiology. Cell physiology 92 16928772
2009 NF-kappaB p50/RelA and c-Rel-containing dimers: opposite regulators of neuron vulnerability to ischaemia. Journal of neurochemistry 91 19094066
1999 Control of development and immunity by rel transcription factors in Drosophila. Oncogene 91 10602463
2005 NF-kappaB factor c-Rel mediates neuroprotection elicited by mGlu5 receptor agonists against amyloid beta-peptide toxicity. Cell death and differentiation 89 15818410
2020 c-Rel Is a Myeloid Checkpoint for Cancer Immunotherapy. Nature cancer 85 33458695
1995 FK506 inhibits antigen receptor-mediated induction of c-rel in B and T lymphoid cells. The Journal of experimental medicine 83 7532676
2011 NF-κB/Rel: agonist and antagonist roles in HIV-1 latency. Current opinion in HIV and AIDS 79 21242888
1990 Structure and autoregulation of the c-rel promoter. Oncogene 76 2284104
2012 Late-onset Parkinsonism in NFκB/c-Rel-deficient mice. Brain : a journal of neurology 74 22915735
2011 The NF-κB subunit c-Rel stimulates cardiac hypertrophy and fibrosis. The American journal of pathology 72 22210479
2007 MALT1 directs B cell receptor-induced canonical nuclear factor-kappaB signaling selectively to the c-Rel subunit. Nature immunology 71 17660823
1999 Interactions between an HMG-1 protein and members of the Rel family. Proceedings of the National Academy of Sciences of the United States of America 71 10485885
2004 Specific NEMO mutations impair CD40-mediated c-Rel activation and B cell terminal differentiation. The Journal of clinical investigation 70 15578091
1994 Developmental expression of the mouse c-rel proto-oncogene in hematopoietic organs. Development (Cambridge, England) 70 7607087
2003 Distinctions between c-Rel and other NF-kappaB proteins in immunity and disease. BioEssays : news and reviews in molecular, cellular and developmental biology 69 12879447
2007 PKCtheta promotes c-Rel-driven mammary tumorigenesis in mice and humans by repressing estrogen receptor alpha synthesis. The Journal of clinical investigation 67 18037997
2007 IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma. Blood 64 17138822
1998 Protein phosphatase X interacts with c-Rel and stimulates c-Rel/nuclear factor kappaB activity. The Journal of biological chemistry 63 9837938
2010 Regulation of the IL-21 gene by the NF-κB transcription factor c-Rel. Journal of immunology (Baltimore, Md. : 1950) 62 20639489
1994 Purification, reconstitution, and I kappa B association of the c-Rel-p65 (RelA) complex, a strong activator of transcription. Molecular and cellular biology 61 8139561
2005 c-Rel-dependent priming of naive T cells by inflammatory cytokines. Immunity 57 16226509
2001 c-Rel is required for the protection of B cells from antigen receptor-mediated, but not Fas-mediated, apoptosis. Journal of immunology (Baltimore, Md. : 1950) 57 11673501
2010 c-Rel but not NF-kappaB1 is important for T regulatory cell development. European journal of immunology 55 20082358
2007 Gains of REL in primary mediastinal B-cell lymphoma coincide with nuclear accumulation of REL protein. Genes, chromosomes & cancer 55 17243160
2002 c-Rel regulation of the cell cycle in primary mouse B lymphocytes. International immunology 55 12147627
2016 A miR-155-Peli1-c-Rel pathway controls the generation and function of T follicular helper cells. The Journal of experimental medicine 54 27481129
2010 The c-Rel subunit of nuclear factor-kappaB regulates murine liver inflammation, wound-healing, and hepatocyte proliferation. Hepatology (Baltimore, Md.) 54 20058312
2014 A small-molecule c-Rel inhibitor reduces alloactivation of T cells without compromising antitumor activity. Cancer discovery 53 24550032
2016 c-Rel and its many roles in cancer: an old story with new twists. British journal of cancer 52 26757421
2019 Caspase-8 promotes c-Rel-dependent inflammatory cytokine expression and resistance against Toxoplasma gondii. Proceedings of the National Academy of Sciences of the United States of America 51 31147458
2012 A key role for NF-κB transcription factor c-Rel in T-lymphocyte-differentiation and effector functions. Clinical & developmental immunology 50 22481964
2004 T cell-intrinsic expression of c-Rel regulates Th1 cell responses essential for resistance to Toxoplasma gondii. Journal of immunology (Baltimore, Md. : 1950) 50 15004174
2020 NF-κB c-Rel Dictates the Inflammatory Threshold by Acting as a Transcriptional Repressor. iScience 48 32062419
2003 Regulation of c-Rel nuclear localization by binding of Ca2+/calmodulin. Molecular and cellular biology 48 12556500
2015 NF-κB1, NF-κB2 and c-Rel differentially regulate susceptibility to colitis-associated adenoma development in C57BL/6 mice. The Journal of pathology 45 25727407
2003 Cyclin E and Bcl-xL cooperatively induce cell cycle progression in c-Rel-/- B cells. Oncogene 45 14627988
2015 Cutting edge: NF-κB p65 and c-Rel control epidermal development and immune homeostasis in the skin. Journal of immunology (Baltimore, Md. : 1950) 44 25681334
1995 Interactions of a Rel protein with its inhibitor. Proceedings of the National Academy of Sciences of the United States of America 43 7479760
1991 The v-rel and c-rel proteins exist in high molecular weight complexes in avian and murine cells. Oncogene 43 1851550
2020 Pro-survival and anti-inflammatory roles of NF-κB c-Rel in the Parkinson's disease models. Redox biology 42 31986466
2019 NF-κB/Rel Transcription Factors in Pancreatic Cancer: Focusing on RelA, c-Rel, and RelB. Cancers 42 31277415
2001 PU.1/Spi-B regulation of c-rel is essential for mature B cell survival. Immunity 42 11672537
1984 Structure and dimorphism of c-rel (turkey), the cellular homolog to the oncogene of reticuloendotheliosis virus strain T. Journal of virology 42 6319751
2010 c-Rel: a pioneer in directing regulatory T-cell lineage commitment? European journal of immunology 41 20162555
2012 Involvement of Notch signaling pathway in regulating IL-12 expression via c-Rel in activated macrophages. Molecular immunology 40 22463790
2014 c-Rel is a critical mediator of NF-κB-dependent TRAIL resistance of pancreatic cancer cells. Cell death & disease 38 25299780
2019 MicroRNA-365a-3p inhibits c-Rel-mediated NF-κB signaling and the progression of pancreatic cancer. Cancer letters 37 30910589
2017 NF-κB1, c-Rel, and ELK1 inhibit miR-134 expression leading to TAB1 upregulation in paclitaxel-resistant human ovarian cancer. Oncotarget 37 28206956
2013 The c-Rel subunit of NF-κB regulates epidermal homeostasis and promotes skin fibrosis in mice. The American journal of pathology 37 23562440
2007 Nuclear CD40 interacts with c-Rel and enhances proliferation in aggressive B-cell lymphoma. Blood 37 17567982
1992 Regulation of human immunodeficiency virus enhancer function by PRDII-BF1 and c-rel gene products. Journal of virology 36 1727488
2018 Circadian control of p75 neurotrophin receptor leads to alternate activation of Nrf2 and c-Rel to reset energy metabolism in astrocytes via brain-derived neurotrophic factor. Free radical biology & medicine 33 29374533
2015 The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma. Oncogene 33 26522720
2014 c-Rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells. The Journal of biological chemistry 32 25266721
2012 Roles of c-Rel signalling in inflammation and disease. The international journal of biochemistry & cell biology 32 22405852
2008 c-Rel is essential for the development of innate and T cell-induced colitis. Journal of immunology (Baltimore, Md. : 1950) 32 18523276
2003 Selective loss of c-Rel compromises dendritic cell activation of T lymphocytes. Cellular immunology 30 12826080
2000 Increased expression of c-rel, from the NF-kappaB/Rel family, in T cells from patients with systemic lupus erythematosus. The Journal of rheumatology 29 10648027
1998 Degradation of proto-oncoprotein c-Rel by the ubiquitin-proteasome pathway. The Journal of biological chemistry 29 9857058
1992 The rel family of proteins. BioEssays : news and reviews in molecular, cellular and developmental biology 29 1533515
2003 Characterization of the stringent response and rel(Bbu) expression in Borrelia burgdorferi. Journal of bacteriology 28 12533471
2002 Genetic evidence for Shc requirement in TCR-induced c-Rel nuclear translocation and IL-2 expression. Proceedings of the National Academy of Sciences of the United States of America 28 11917142
2023 Esmethadone-HCl (REL-1017): a promising rapid antidepressant. European archives of psychiatry and clinical neuroscience 27 36890259
2020 c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis. Nature metabolism 27 33168981
2019 NF-κB/c-Rel deficiency causes Parkinson's disease-like prodromal symptoms and progressive pathology in mice. Translational neurodegeneration 27 31139367
2016 Transcriptional regulation of miR-15b by c-Rel and CREB in Japanese encephalitis virus infection. Scientific reports 26 26931521
2016 Treating psoriasis by targeting its susceptibility gene Rel. Clinical immunology (Orlando, Fla.) 26 26993753
2011 Foxp3 interacts with c-Rel to mediate NF-κB repression. PloS one 26 21490927
2004 Stimulation of c-Rel transcriptional activity by PKA catalytic subunit beta. Journal of molecular medicine (Berlin, Germany) 26 15197457
1989 Expression of the c-rel and c-myc proto-oncogenes in avian tissues. Oncogene 26 2666905
2021 Inherited human c-Rel deficiency disrupts myeloid and lymphoid immunity to multiple infectious agents. The Journal of clinical investigation 24 34623332
2020 Human galectin-16 has a pseudo ligand binding site and plays a role in regulating c-Rel-mediated lymphocyte activity. Biochimica et biophysica acta. General subjects 24 33011338
2011 c-Rel promotes type 1 and type 17 immune responses during Leishmania major infection. European journal of immunology 24 21469108
2019 Generation of Foxp3+CD25- Regulatory T-Cell Precursors Requires c-Rel and IκBNS. Frontiers in immunology 22 31354726
2017 Silencing c-Rel in macrophages dampens Th1 and Th17 immune responses and alleviates experimental autoimmune encephalomyelitis in mice. Immunology and cell biology 22 28202908
1998 Distinct domains of IkappaBalpha regulate c-Rel in the cytoplasm and in the nucleus. Molecular and cellular biology 22 9488436
1991 A member of the set of kappa B binding proteins, HIVEN86A, is a product of the human c-rel proto-oncogene. Oncogene 22 2030915
2021 Negative regulation of FOXP3 expression by c-Rel O-GlcNAcylation. Glycobiology 21 33442719
2012 NF-κB p65 and c-Rel subunits promote phagocytosis and cytokine secretion by splenic macrophages in cirrhotic patients with hypersplenism. The international journal of biochemistry & cell biology 21 23195252

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