Affinage

RELB

Transcription factor RelB · UniProt Q01201

Length
579 aa
Mass
62.1 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 43 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

RelB is an NF-κB family transcription factor that controls immune organ development, dendritic cell and osteoclast differentiation, and stress/cancer gene programs through κB-dependent transcription (PMID:1732739, PMID:7834753, PMID:7845467, PMID:18322009). It carries a C-terminal transactivation domain and cannot bind κB DNA as a monomer; instead it forms transactivating heterodimers with p50 and p52, with crystallographic work showing p52:RelB engages a broader spectrum of κB sites (including AT-rich elements) than p50:RelA via RelB Arg125 (PMID:1732739, PMID:8183565, PMID:19098713). RelB is held inactive in the cytosol through direct association with the NF-κB2 precursor p100, which acts as a dedicated IκB-like inhibitor via a region encompassing a nuclear export signal; NIK/IKKα-dependent p100 processing in the noncanonical (LTβR-driven) pathway releases p52:RelB for nuclear import through RelB's own bipartite NLS and importin α5/α6 (PMID:11687592, PMID:12709443, PMID:12505990, PMID:18462924). RelB also forms transcriptionally inactive complexes with RelA/p65 that fail to bind κB DNA and dampen canonical NF-κB responses, a mechanism exploited during endotoxin tolerance (PMID:12657634, PMID:16951372). Its activity is shaped by signal-specific post-translational control: phosphorylation at Thr84/Ser552 triggers proteasomal degradation after T-cell activation, MALT1 cleaves RelB after Arg-85 to license canonical NF-κB DNA binding, PAK4 phosphorylates Ser151 and ERK1 phosphorylation sustains nuclear RelB activity, and Ser368 governs dimerization (PMID:12874295, PMID:11781828, PMID:21873235, PMID:26455434, PMID:31399573). Developmentally, RelB acts largely in radiation-resistant stromal cells to build splenic germinal centers, follicular dendritic cell networks, marginal zones, thymic medulla and lymph-node stroma, and to drive homing chemokine expression, while acting downstream of NIK in osteoclast precursors and as a direct Runx2 repressor in osteoblasts (PMID:7834753, PMID:7845467, PMID:11489970, PMID:18322009, PMID:22940098, PMID:24115294, PMID:28348230). RelB pairs with the aryl hydrocarbon receptor to drive non-canonical target genes including IL-8, BAFF and BLC, and recruits chromatin regulators such as Daxx/Dnmt1 and HDAC4 to repress target loci (PMID:17823304, PMID:17900530, PMID:18413714, PMID:26455434). In cancer it functions as a survival and resistance factor, transcriptionally upregulating MnSOD, PD-L1 (CD274), GPX4, and Bcl-2 to confer radioresistance, immune evasion, ferroptosis resistance, and an invasive phenotype (PMID:16261162, PMID:17369819, PMID:35177112, PMID:37944384).

Mechanistic history

Synthesis pass · year-by-year structured walk · 41 steps
  1. 1992 High

    Established that RelB is a transactivator rather than an inhibitor, defining its core biochemical mode as a heterodimer-dependent activator of κB transcription.

    Evidence GAL4-RelB fusion activation assays, EMSA, and reporter assays showing RelB requires p50 heterodimerization to bind κB sites

    PMID:1732739

    Open questions at the time
    • Did not define which physiological signals control RelB dimer formation
    • Did not address p52 partnering or in vivo relevance
  2. 1994 Medium

    Confirmed that human RelB behaves like its murine counterpart, forming transactivating heterodimers with p50 and p52, extending the activator model across species.

    Evidence Transfection reporter assays and EMSA of human RelB (I-Rel) heterodimeric complexes

    PMID:8183565

    Open questions at the time
    • Single lab, did not address regulation or knockout phenotype
    • p52 vs p50 functional differences not resolved
  3. 1995 High

    Demonstrated the non-redundant in vivo role of RelB in thymic medulla and dendritic cell development, linking the transcription factor to immune homeostasis.

    Evidence relB germline knockout mice with EMSA, histology, and contact sensitivity assays; replicated by an independent lab

    PMID:7834753 PMID:7845467

    Open questions at the time
    • Did not distinguish cell-intrinsic from cell-extrinsic requirements
    • Molecular target genes underlying phenotypes unknown
  4. 1996 High

    Showed the inflammatory and myeloid phenotypes of RelB-deficient mice are T-cell dependent, reframing the defect as dysregulated immune cross-talk rather than a purely cell-autonomous lesion.

    Evidence Genetic epistasis with RelB-KO × RAG-1-KO and RelB-KO × Nur77-Tg double-mutant mice

    PMID:8892630

    Open questions at the time
    • Did not identify the stromal vs hematopoietic source of the requirement
    • Mechanism of aberrant T-cell activation unresolved
  5. 1997 High

    Identified RelB as a negative regulator of chemokine expression in fibroblasts, revealing a repressive arm of its activity distinct from transactivation.

    Evidence LPS stimulation of RelB-KO fibroblasts with EMSA, chemokine quantification, and RelB cDNA rescue plus in vivo recruitment assay

    PMID:9250151

    Open questions at the time
    • Mechanism of chemokine repression (dimer composition) not defined
    • Did not identify direct promoter targets
  6. 2001 High

    Defined p100 as the dedicated cytoplasmic inhibitor of RelB and tied its release to NIK/IKKα-driven p100 processing, establishing RelB as the effector of the noncanonical pathway.

    Evidence Co-IP, nuclear fractionation, p100 deletion mapping, and NIK overexpression

    PMID:11687592

    Open questions at the time
    • Did not resolve how RelB selects p50 vs p52 partners after release
    • Kinetics of processing in physiological signaling not addressed
  7. 2001 High

    Showed RelB is a transcriptional target of RelA, explaining the delayed kinetics of RelB activity as transcriptional induction rather than IκB-mediated retention.

    Evidence RELB promoter cloning, EMSA at κB sites, and TNF/LPS time-course with nuclear fractionation

    PMID:11753650

    Open questions at the time
    • Did not address additional promoter inputs (AP-1, hormone receptors)
    • Cross-talk with p100-mediated retention not integrated
  8. 2001 Medium

    Mapped Ser368 as essential for RelB dimerization and showed RelB feedback-inhibits its own p100 processing, revealing a self-limiting regulatory loop.

    Evidence Site-directed mutagenesis (S368A/D), co-IP, and pulse-chase of p100 stability in plasmacytoma cells

    PMID:12874295

    Open questions at the time
    • Single lab
    • Physiological consequence of the feedback loop in vivo untested
  9. 2001 High

    Established signal-specific proteasomal turnover of RelB driven by Thr84/Ser552 phosphorylation upon T-cell activation, introducing degradative control of RelB stability.

    Evidence T84A/S552A phosphosite mutagenesis, proteasome inhibition, and TCR/TPA stimulation of T cells

    PMID:11781828

    Open questions at the time
    • Kinase(s) for Thr84/Ser552 not identified
    • Relationship to the later-defined N-terminal MALT1 cleavage unclear
  10. 2003 High

    Distinguished two p100-based mechanisms for signal-specific RelB control — IKKα-dependent processing under LTβR vs TNF-induced p100–RelB/p50 sequestration — clarifying how distinct stimuli route RelB.

    Evidence IKK and RelA knockout MEFs with EMSA and Co-IP under LTβR vs TNF stimulation; complementary NIK/NF-κB2 knockout in vivo work

    PMID:12505990 PMID:12709443

    Open questions at the time
    • Did not define molecular basis of TNF-induced sequestration
    • Cell-type specificity of the two mechanisms unresolved
  11. 2003 High

    Identified inhibitory RelA·RelB heterodimers that cannot bind κB DNA, providing a mechanism by which RelB restrains canonical NF-κB output.

    Evidence Reporter assays, EMSA with in vitro translated proteins, Co-IP, and RelB overexpression in MEFs

    PMID:12657634

    Open questions at the time
    • In vivo significance and stoichiometry of the dimer not established
    • Structural basis of DNA-binding incompetence not defined
  12. 2003 High

    Showed RelB requires stromal-cell expression to build germinal centers, FDC networks, and marginal zones, separating cell-extrinsic architectural roles from hematopoietic functions.

    Evidence Reciprocal bone marrow chimeras, immunofluorescence, and chemokine RT-PCR in RelB-KO spleen

    PMID:11489970

    Open questions at the time
    • Direct stromal target genes beyond BLC not mapped
    • Mechanism of FDC patterning unresolved
  13. 2003 High

    Demonstrated RelB acts in stromal cells downstream of NIK for dendritic cell-mediated NKT cell development, providing in vivo genetic evidence for a NIK–RelB axis.

    Evidence RelB-KO and aly/aly NIK-mutant mice, bone marrow chimeras, compound heterozygous epistasis, and in vitro NIK kinase assay

    PMID:12810685

    Open questions at the time
    • Direct NIK phosphorylation target in the pathway not pinpointed
    • Stromal RelB target genes for NKT development unknown
  14. 2003 High

    Showed RelB transcription is directly repressed by vitamin D via VDR·RXRα binding to relB promoter VDREs, identifying a hormonal brake on RelB independent of NF-κB signaling.

    Evidence VDRE identification, gel shift, reporter assays with VDRE mutagenesis, and VDR-KO mouse comparison

    PMID:14507914

    Open questions at the time
    • Did not yet define the chromatin co-repressor machinery
    • Physiological context of vitamin D repression unaddressed
  15. 2005 High

    Defined the chromatin mechanism of vitamin D repression of RelB as VDR-recruited HDAC3, connecting hormonal signaling to histone deacetylation at the relB promoter.

    Evidence ChIP, HDAC inhibitor assays, HDAC3 overexpression/knockdown, and in vivo VDR-KO mice

    PMID:16239345

    Open questions at the time
    • Did not address LPS-induced reversal mechanism in detail
    • Generalizability beyond dendritic cells unknown
  16. 2006 Medium

    Linked IKKα-driven p52/RelB transcription to cell-cycle control via Skp2/p27Kip1, extending RelB function into proliferation in cancer cells.

    Evidence IKKα siRNA, ChIP at the skp2 promoter, reporter assays, and cell cycle analysis in pancreatic cancer cells

    PMID:16902410

    Open questions at the time
    • Single lab
    • Direct RelB occupancy vs IKKα-mediated indirect effects not fully separated
  17. 2006 Medium

    Identified RelB as a driver of antioxidant defense and radioresistance through MnSOD upregulation, establishing a cytoprotective role in cancer therapy resistance.

    Evidence Dominant-negative p100, RelB siRNA, MnSOD Western blot, and clonogenic radiation survival assay in prostate cancer cells

    PMID:16261162

    Open questions at the time
    • Direct RelB binding at the MnSOD promoter not shown here
    • Single lab
  18. 2006 Medium

    Showed RelB induction during endotoxin tolerance represses proinflammatory genes via inactive p65/RelB dimers, providing a mechanistic basis for tolerance.

    Evidence THP-1 tolerance model with RelB siRNA rescue, Co-IP of p65/RelB, EMSA, and reporter assays

    PMID:16951372

    Open questions at the time
    • Single lab
    • Genome-wide scope of RelB-mediated repression undefined
  19. 2007 High

    Discovered the RelB–AhR complex binding novel response elements to drive IL-8 and immune genes, revealing a non-canonical, ARNT-independent transcriptional partnership.

    Evidence Reciprocal Co-IP, ChIP at IL-8 promoter, reporter assays, PKA modulation, and EMSA; corroborated by AhR/RelB occupancy on BAFF, BLC, CCL1, IRF3 promoters

    PMID:17823304 PMID:17900530

    Open questions at the time
    • Stoichiometry and DNA-binding subunit of the RelB/AhR complex unresolved
    • Physiological xenobiotic contexts incompletely defined
  20. 2007 High

    Defined constitutive RelB synthesis in ERα-negative breast cancer via NF-κB/AP-1 promoter synergy and its pro-invasive output through Bcl-2, embedding RelB in tumor aggressiveness.

    Evidence EMSA, ChIP, promoter mutagenesis reporters, siRNA, invasion assays, and breast tumor IHC correlation

    PMID:17369819

    Open questions at the time
    • Did not establish the ERα-RelB reciprocal loop mechanism (addressed later)
    • Single tumor type
  21. 2008 High

    Provided the structural basis for RelB's distinct DNA-site preference, showing p52:RelB accommodates AT-rich κB sites via Arg125, explaining target-gene selectivity.

    Evidence X-ray crystallography of the p52:RelB:κB DNA complex with Arg125A mutagenesis, EMSA, and reporter assays

    PMID:19098713

    Open questions at the time
    • Structure of RelB with other partners (RelA, p50) not solved
    • Genome-wide consequences of broadened site preference untested
  22. 2008 Medium

    Defined RelB's intrinsic bipartite NLS and importin α5/α6 usage, showing RelB nuclear import drives p52/RelB translocation independent of the p52 NLS.

    Evidence In vitro importin binding assays and NLS-mutant RelB nuclear translocation assays

    PMID:18462924

    Open questions at the time
    • Single lab
    • Regulation of NLS exposure by p100 not mechanistically linked
  23. 2008 High

    Showed RelB stability depends on multi-domain contacts with p100/p105/p52/p50, establishing that the same precursor proteins both inhibit and protect RelB.

    Evidence Co-IP, domain mapping of p100 and RelB, and Western blot in p100-KO and p100/p105 double-KO cells

    PMID:18321863

    Open questions at the time
    • Quantitative contribution of each domain to half-life not defined
    • Link between stabilization and degradative phosphorylation pathways unresolved
  24. 2008 High

    Identified Daxx/Dnmt1-mediated DNA hypermethylation as a RelB-dependent mechanism for epigenetic silencing of RelB target genes, expanding RelB into chromatin-level gene control.

    Evidence ChIP, bisulfite methylation analysis, daxx-KO/relB-KO cells with rescue, and Daxx/Dnmt1 Co-IP

    PMID:18413714

    Open questions at the time
    • Signals controlling Daxx recruitment to RelB sites unknown
    • Generality across RelB target sets undefined
  25. 2008 High

    Established RelB as the essential NF-κB effector downstream of NIK for osteoclast differentiation, with p100 deletion bypassing the NIK requirement.

    Evidence NIK-KO/RelB-KO mice, p100-KO epistasis, retroviral RelB vs p65 rescue, osteoclast differentiation assays, and in vivo TNFα challenge

    PMID:18322009

    Open questions at the time
    • Direct RelB osteoclastogenic target genes not mapped here
    • Dimer partner in osteoclast precursors not defined
  26. 2009 Medium

    Defined the reciprocal RelB–ERα antagonism via RelB-induced Blimp1 repression of ESR1, mechanistically connecting RelB activation to estrogen-independent breast cancer.

    Evidence RelB siRNA, ESR1/PRDM1 reporter assays, ChIP, and migration assays in breast cancer lines

    PMID:19433448

    Open questions at the time
    • Single lab
    • Direct vs indirect RelB control of PRDM1 not fully resolved
  27. 2010 Medium

    Identified REQ/DPF2 as an adaptor linking p52 to the Brm SWI/SNF complex at the BLC promoter, showing RelB/p52 recruits chromatin-remodeling machinery for target activation.

    Evidence In vitro binding, Co-IP, ChIP at the BLC promoter, REQ/Brm knockdown, and soft-agar growth assay

    PMID:20460684

    Open questions at the time
    • Single lab
    • Generality of REQ-dependent remodeling across RelB targets untested
  28. 2011 High

    Discovered MALT1 cleavage of RelB after Arg-85 as a switch that licenses canonical NF-κB DNA binding, mechanistically integrating RelB into lymphoma signaling.

    Evidence In vitro MALT1 cleavage assay with MS site identification, proteasome rescue, and RelB overexpression in DLBCL lines with reporter/EMSA

    PMID:21873235

    Open questions at the time
    • Upstream regulators of MALT1-RelB cleavage only partly defined
    • In vivo physiological scope beyond DLBCL unaddressed
  29. 2012 High

    Revealed that during DC activation RelB operates as a canonical-IκB-controlled RelB–p50 dimer rather than the expected p52 effector, refining the pathway logic of RelB control.

    Evidence IκBα-KO, IκBε-KO, p52-KO mice, ChIP, Western blot, and computational modeling validated in engineered fibroblasts

    PMID:23086447

    Open questions at the time
    • Cell types where RelB-p52 dominates vs RelB-p50 not fully delineated
    • Quantitative dimer partitioning in vivo unresolved
  30. 2012 Medium

    Showed the NF-κB2–RelB pathway blocks adipogenesis and redirects mesenchymal precursors toward lymph-node stroma, extending RelB into stromal cell-fate decisions.

    Evidence LTβR-KO and NF-κB2/RelB genetic models with in vivo organogenesis and precursor transplantation assays

    PMID:22940098

    Open questions at the time
    • Single lab
    • Direct RelB target genes controlling adipogenic suppression not mapped
  31. 2012 Medium

    Identified hypercapnia-induced proteasome-dependent RelB cleavage independent of GSK3β/MALT1, indicating a distinct stimulus-specific processing route.

    Evidence Western blot for cleavage product, nuclear fractionation, MG-132, GSK3β inhibitor, MALT1 deficiency, and in vivo lung injury model

    PMID:22396550

    Open questions at the time
    • Protease responsible for hypercapnia-induced cleavage unidentified
    • Functional transcriptional consequences not fully defined
  32. 2014 Medium

    Established RelB as a direct repressor of Runx2 limiting osteoblast differentiation, complementing its osteoclast role to define bidirectional control of bone.

    Evidence RelB-KO mice, ChIP at the Runx2 promoter, reporter assays, osteoblast differentiation, and bone defect transplantation

    PMID:24115294

    Open questions at the time
    • Single lab
    • Dimer partner mediating Runx2 repression not identified
  33. 2015 High

    Defined an HDAC4–RelB–p52 repressive complex sustaining myeloma survival via Bim/BMF silencing and identified ERK1 as a RelB kinase maintaining nuclear activity, adding a kinase-driven survival mechanism.

    Evidence HDAC4–RelB Co-IP, ChIP at Bim/BMF, HDAC4-mimetic peptide disruption, ERK1 kinase assay, and xenograft growth assay

    PMID:26455434

    Open questions at the time
    • ERK1 phosphosite on RelB not specified
    • Generality of HDAC4-RelB axis beyond myeloma unknown
  34. 2015 Medium

    Showed RelB/p50 (not p65) directly drives cytokine-induced YKL-40 expression in astrocytes, demonstrating RelB-specific transcriptional control in CNS inflammation.

    Evidence ChIP at the YKL-40 promoter, NF-κB-site mutagenesis reporters, p65 vs RelB/p50 manipulation, and Co-IP in primary astrocytes

    PMID:25681350

    Open questions at the time
    • Single lab
    • Upstream signaling controlling RelB/p50 formation only partly defined
  35. 2016 High

    Identified PAK4-mediated Ser151 phosphorylation as critical for RelB DNA binding, linking a kinase to RelB transcriptional activity and senescence control in breast cancer.

    Evidence PAK4 kinase assay on RelB, S151A phospho-mutant, ChIP, knockdowns, and MMTV-PAK4/PyMT mouse models

    PMID:31399573

    Open questions at the time
    • Interplay between Ser151, Ser368, and degradative phosphosites unresolved
    • Tissue scope of PAK4-RelB axis beyond breast not defined
  36. 2016 Medium

    Showed Relb acts downstream of mTEC stem cells to generate RANK+ mTEC progenitors, refining its developmental position in thymic epithelial differentiation.

    Evidence RANK Venus reporter and Relb-KO/nude mice with flow cytometry and thymic histology

    PMID:26806881

    Open questions at the time
    • Single lab
    • Direct RelB target genes in mTEC progenitor emergence unknown
  37. 2017 High

    Dissected cell-intrinsic vs extrinsic RelB requirements in cDC development, attributing most defects to stromal RelB while assigning intrinsic RelB to a specific cDC2 subset.

    Evidence Systematic reciprocal radiation chimeras with DC-subset flow cytometry

    PMID:28348230

    Open questions at the time
    • Stromal RelB target genes governing DC homeostasis not mapped
    • Molecular basis of the Notch2/LTβR-dependent cDC2 requirement undefined
  38. 2018 High

    Established the LTβ–RELB axis as the driver of cholangiocyte ductular reaction and biliary fibrosis downstream of CYLD loss, extending RelB into liver disease pathology.

    Evidence Cyld/Relb double-KO mice, DDC diet model, RELB siRNA in human cholangiocytes with LTβR agonist, and ChIP

    PMID:30445013

    Open questions at the time
    • Direct RelB fibrogenic target genes not detailed
    • Translational relevance to human cholangiopathies untested
  39. 2018 Medium

    Linked GSK3β to RelB turnover through BCL10 phosphorylation and CBM complex assembly, identifying an upstream modulator of MALT1-mediated RelB cleavage.

    Evidence GSK3β inhibitors and siRNA, Western blot for RelB proteolysis, NF-κB reporters, and CBM complex Co-IP

    PMID:29358699

    Open questions at the time
    • Single lab
    • Direct GSK3β substrate phosphosite on BCL10 vs other CBM components not fully resolved
  40. 2022 Medium

    Identified RelB as a direct transcriptional activator of PD-L1, establishing a mechanism for RelB-driven tumor immune evasion.

    Evidence ChIP at CD274 promoter, promoter-mutagenesis reporters, RelB knockdown, T-cell co-culture cytotoxicity, and xenograft/metastasis models

    PMID:35177112

    Open questions at the time
    • Single lab
    • Dimer partner driving CD274 transcription not defined
  41. 2023 Medium

    Showed RelB confers tamoxifen resistance by upregulating GPX4 and suppressing ferroptosis, linking RelB to redox-dependent therapy resistance.

    Evidence ChIP at GPX4 promoter, reporter assays, RelB/GPX4 knockdown, ferroptosis assays, and xenograft models

    PMID:37944384

    Open questions at the time
    • Single lab
    • Upstream signals activating RelB in resistant cells not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple phosphorylation marks (Thr84/Ser552, Ser151, Ser368, ERK1 sites), MALT1 cleavage, and p100-mediated stabilization are integrated into a single regulatory logic that selects RelB dimer partner, stability, and target-gene program in a given cell remains unresolved.
  • No unified model linking PTMs to dimer choice and target selection
  • Genome-wide RelB cistrome across cell types and stimuli not defined
  • Structural basis of RelA·RelB inactive dimers unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2 GO:0005829 cytosol 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
AHRDAXXDPF2HDAC4MALT1NFKB1/P50NFKB2/P100/P52RELA
Complex memberships
HDAC4–RelB–p52 repressor complexRelB:RelA (inactive) heterodimerRelB:p50 NF-κB heterodimerRelB:p52 NF-κB heterodimer

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 RelB contains a C-terminal transcriptional activation domain (last 180 amino acids) and does not bind NF-κB sites as a monomer, but forms heterodimers with p50-NF-κB that bind κB sites and transactivate κB-dependent promoters, unlike p50 homodimers which cannot transactivate. GAL4-RelB fusion transcriptional activation assays in yeast; EMSA; reporter gene (transactivation) assays Molecular and cellular biology High 1732739
1994 Human RelB (I-Rel) forms κB-binding heterodimeric complexes with p50 and p52 that potently transactivate κB-dependent constructs; it functions as a transactivator, not an inhibitor, consistent with murine RelB. Transfection reporter assays; EMSA with heterodimeric complexes Oncogene Medium 8183565
1995 RelB is required for development of thymic medulla and dendritic cells; germline disruption of relB results in absence of RelB protein, dramatic reduction of constitutive κB-binding activity in thymus/spleen, loss of thymic dendritic cells, multiorgan inflammation, myeloid hyperplasia, and impaired cellular immunity. Targeted gene disruption (knockout mouse); EMSA; histology; contact sensitivity assays Cell High 7834753 7845467
1996 Both multiorgan inflammation and myeloid hyperplasia in RelB-deficient mice are T cell dependent: RelB-KO × RAG-1-KO and RelB-KO × Nur77/N10-Tg mice are disease-free; B cells are not required for the phenotype. Genetic epistasis using double-mutant mice (RelB-KO × RAG-1-KO; RelB-KO × Nur77/N10-Tg; RelB-KO × p50-KO); histology Journal of immunology High 8892630
1997 RelB is an important regulator of chemokine expression in fibroblasts: RelB-deficient fibroblasts show persistent, dramatically elevated expression of seven chemokines (RANTES, MIP-1α, MIP-1β, MIP-2, IP-10, JE/MCP-1, KC/CINC) after LPS stimulation, correlated with increased NF-κB binding; transfection of RelB cDNA into RelB-deficient fibroblasts reversed this overexpression. RelB-KO fibroblast LPS stimulation; EMSA; chemokine measurement; RelB cDNA rescue transfection; in vivo granulocyte recruitment assay The American journal of pathology High 9250151
2001 RelB is associated in the cytosol with p100 (NF-κB2 precursor), not with IκBα, IκBβ, IκBε, or p105; p100 prevents RelB nuclear localization and transcriptional activity via amino acids 623–900 of p100, which contain a nuclear export signal; NF-κB-inducing kinase (NIK) overexpression, which promotes p100 processing via IKKα, induces RelB nuclear translocation. Co-immunoprecipitation; nuclear fractionation; reporter assays; structure–function analysis of p100 deletion mutants; NIK overexpression The Journal of biological chemistry High 11687592
2001 RelA alone is sufficient to induce RelB gene transcription via a TATA-less promoter containing two NF-κB binding sites; the delayed nuclear translocation of RelB after TNF or LPS stimulation is secondary to increased RelB transcription, not to IκB-mediated cytosolic retention. Promoter cloning; reporter assays; EMSA with promoter κB sites; TNF/LPS stimulation time-course; nuclear fractionation Oncogene High 11753650
2001 RelB is required for germinal center formation, follicular dendritic cell networks, and marginal zone organization in spleen; reciprocal bone marrow transfers demonstrate that RelB expression in radiation-resistant stromal cells (not hematopoietic cells) is required for GCs, FDC networks, and MZ structures, whereas RelB in hematopoietic cells is required for MZ B cell generation. RelB-dependent homing chemokine expression (especially BLC) is strongly reduced in RelB-deficient spleen. RelB-KO mice; reciprocal bone marrow chimeras; immunofluorescence; RT-PCR for chemokines Journal of immunology High 11489970
2001 RelB serine 368 is critical for dimerization with other NF-κB family members but not for nuclear import; expression of functional RelB strongly reduces p52 generation and increases expression of p100 precursor by prolonging p100 half-life, suggesting RelB inhibits p100 processing. Site-directed mutagenesis (S368A/D); co-immunoprecipitation; Western blot for p100/p52; pulse-chase analysis of p100 stability in S107 plasmacytoma cells The Journal of biological chemistry Medium 12874295
2001 RelB undergoes signal-specific, proteasomal degradation upon T cell activation (TCR or TPA/ionomycin) but not TNFα stimulation; degradation proceeds through phosphorylation at Thr84 and Ser552, followed by an N-terminal cleavage, then complete proteasomal degradation; mutation of both phosphoacceptor sites stabilizes RelB. Phosphorylation site mutagenesis (T84A/S552A double mutant); Western blot; proteasome inhibitor treatment; TCR/TPA stimulation of T cells Oncogene High 11781828
2003 LTβR signaling induces RelB/p50 and RelA/p50 heterodimers, whereas TNF activates only RelA/p50; LTβR-induced RelB/p50 binding requires p100 processing mediated by IKKα but not IKKβ, NEMO/IKKγ, or RelA; TNF increases p100–RelB/p50 nuclear association, specifically inhibiting RelB DNA binding, providing two distinct p100-dependent mechanisms for signal-specific RelB regulation. Deficient MEF cells (IKKα-KO, IKKβ-KO, IKKγ-KO, RelA-KO); EMSA; Co-IP; LTβR and TNF stimulation The Journal of biological chemistry High 12709443
2003 RelB forms transcriptionally inactive heterodimers with RelA/p65; these RelA·RelB dimers are unable to bind κB DNA in vitro; overexpressed RelB significantly reduces TNFα-induced RelA activity; these complexes are not regulated by IκB proteins and are found in both cytoplasm and nucleus. Reporter gene assays; EMSA with in vitro translated proteins; co-immunoprecipitation; overexpression in MEFs The Journal of biological chemistry High 12657634
2003 LTβR signaling activates p52-RelB heterodimers via NIK- and IKKα-dependent (but IKKβ- and IKKγ-independent) processing of p100; TNF activates RelA but specifically inhibits RelB by increasing p100–RelB/p50 complex formation; RelB/p52 is required for Peyer's patch development downstream of LTβR. Knockout mice (NF-κB2-KO, RelB-KO, LTβR-KO, NIK-mutant); EMSA; Western blot for p100/p52; genetic epistasis in vivo The EMBO journal High 12505990
2003 RelB stabilizes itself through direct interaction with p100 (all domains engaged), p105, p52, and p50; p100–RelB complex formation requires unique N-terminal domain contacts and RelB's transcriptional activation domain interacting with p100's processing region; RelB protein levels are significantly reduced in the absence of p100 and further reduced when both p100 and p105 are absent. Co-immunoprecipitation; domain deletion/mutagenesis of p100 and RelB; Western blot in p100-KO and p100/p105-double-KO cells The Journal of biological chemistry High 18321863
2003 RelB is the NF-κB subunit required for dendritic cell-mediated NKT cell development via a NIK-dependent pathway; RelB must be expressed in irradiation-resistant, CD1d-negative host stromal cells (not hematopoietic cells) for NKT cell development; compound heterozygous RelB+/− × aly/+ mice have reduced NKT cell responses, demonstrating in vivo genetic interaction between NIK and RelB. RelB-KO and NIK-mutant (aly/aly) mice; bone marrow chimeras; compound heterozygous epistasis; flow cytometry; in vitro NIK kinase assay with RelB activation readout The Journal of experimental medicine High 12810685
2003 1α,25-dihydroxyvitamin D3 (and analogs) directly represses RelB transcription through VDR·RXRα binding to vitamin D response elements in the relB promoter; mutagenesis of these VDREs abolishes suppression; NF-κB response element mutagenesis does not affect vitamin D suppression, ruling out indirect NF-κB effects. Promoter VDRE identification; gel shift assays (VDR·RXRα binding); reporter assays with VDRE mutagenesis; VDR overexpression; DC-derived cell lines; in vivo VDR-KO mouse comparison The Journal of biological chemistry High 14507914
2005 Vitamin D receptor-mediated relB promoter suppression in dendritic cells involves direct VDR binding to the relB promoter and recruitment of HDAC3 (but not HDAC1 alone); HDAC3 association is enhanced by D3 ligand and reduced by LPS; HDAC3 overexpression causes relB suppression, and HDAC3 depletion attenuates D3-mediated suppression. Chromatin immunoprecipitation (ChIP); HDAC inhibitor experiments; HDAC3 overexpression/siRNA knockdown; promoter reporter assays; in vivo VDR-KO mice Proceedings of the National Academy of Sciences High 16239345
2006 IKKα regulates G1-to-S phase progression in pancreatic cancer cells by controlling p52/RelB-dependent transcription of the skp2 gene, which in turn regulates Skp2-mediated degradation of p27Kip1; IKKα siRNA increases p27 protein by downregulating Skp2. IKKα-specific siRNA; Western blot for p27/Skp2; ChIP at skp2 promoter for RelB/p52; reporter assays; cell cycle analysis The EMBO journal Medium 16902410
2006 RelB transcriptionally upregulates manganese superoxide dismutase (MnSOD) gene in aggressive prostate cancer cells; selective inhibition of RelB (by dominant-negative p100 mutant or siRNA) decreases MnSOD levels and significantly increases radiation sensitivity of prostate cancer cells. Dominant-negative p100 mutant; siRNA knockdown of RelB; Western blot for MnSOD; clonogenic radiation survival assay Oncogene Medium 16261162
2006 RelB induction during LPS endotoxin tolerance represses proinflammatory gene expression (e.g., IL-1β, TNFα); tolerant cells form transcriptionally inactive NF-κB p65/RelB heterodimers; siRNA knockdown of RelB in tolerant THP-1 cells restores endotoxin induction of IL-1β. THP-1 endotoxin tolerance model; RelB siRNA; reporter assays; co-immunoprecipitation of p65/RelB complexes; EMSA Journal of immunology Medium 16951372
2007 RelB physically interacts with the aryl hydrocarbon receptor (AhR); the RelB/AhR complex binds a novel RelB/AhR responsive element in the IL-8 promoter (distinct from classical DRE or κB sites) as well as xenobiotic responsive elements; AhR ligand TCDD promotes time-dependent recruitment of AhR to the RelB/AhR element via protein kinase A; RelB markedly increases TCDD-induced XRE reporter activity. Co-immunoprecipitation (RelB–AhR); ChIP (time-dependent AhR recruitment to IL-8 promoter); reporter assays; PKA inhibitor/activator experiments; EMSA Molecular endocrinology High 17823304
2007 Constitutive de novo RelB synthesis in ERα-negative invasive breast cancer cells is driven by p50-p65 NF-κB and c-Jun–Fra-2 AP-1 complexes binding to the RELB promoter in synergy; ERα signaling inhibits RelB synthesis by reducing NF-κB and Fra-2 levels; RelB induces Bcl-2 to promote the invasive phenotype. EMSA; ChIP; reporter assays with promoter mutagenesis; siRNA knockdown; invasion assays; IHC correlation in breast cancer tissues Nature cell biology High 17369819
2007 AhR/RelB complexes bind NF-κB elements on BAFF, BLC, CCL1, and IRF3 promoters in an ARNT-independent manner to drive their expression; TCDD induces this binding and gene expression in a RelB- and AhR-dependent manner in U937 macrophages. EMSA; ChIP; siRNA knockdown of AhR and RelB; RT-PCR for target gene expression; TCDD treatment Biochemical and biophysical research communications Medium 17900530
2008 The NF-κB p52:RelB heterodimer crystal structure reveals Arg125 of RelB contacts an additional DNA base pair; p52:RelB Arg125A mutant shows defective DNA binding and transcriptional activity selectively at κB sites with contiguous central A:T base pairs; p52:RelB binds a broader spectrum of κB sites than p50:RelA due to its ability to accommodate structural variation at AT-rich sites. X-ray crystallography of p52:RelB:κB DNA complex; site-directed mutagenesis (Arg125A); EMSA; transcriptional reporter assays EMBO reports High 19098713
2008 RelB has a bipartite arginine/lysine-rich NLS that mediates binding to importin α5 and α6 for nuclear import; nuclear import of p52/RelB heterodimers is mediated exclusively by the RelB NLS, not the p52 NLS. In vitro binding assays with importin α isoforms; nuclear translocation assays; NLS-mutant RelB constructs; viral infection and TNF stimulation models Cellular signalling Medium 18462924
2008 Daxx represses RelB target genes (dapk1, dapk3, c-flip, birc3/ciap2) by recruiting DNA methyltransferase 1 (Dnmt1) to their promoters in a RelB-dependent manner, resulting in DNA hypermethylation; methylation of target promoters is decreased in daxx-KO cells and restored by re-introduction of Daxx. ChIP; bisulfite sequencing/methylation analysis; daxx-KO and relB-KO cells; Daxx/Dnmt1 co-immunoprecipitation; reporter assays; stable transfection rescue Genes & development High 18413714
2008 RelB is required for osteoclast differentiation downstream of NIK; deletion of p100 restores differentiation of NIK-deficient OC precursors; overexpression of RelB (but not p65) rescues NIK-deficient precursors; RelB-KO precursors fail to form OCs and this defect is rescued specifically by RelB re-expression; RelB-KO mice show diminished osteoclastogenic response to TNFα in vivo. NIK-KO and RelB-KO mice; p100-KO epistasis; retroviral overexpression of RelB vs p65; in vitro osteoclast differentiation assays; in vivo TNFα challenge; B16 melanoma bone tumor model Proceedings of the National Academy of Sciences High 18322009
2009 RelB NF-κB reciprocally inhibits estrogen receptor α (ERα) synthesis in breast cancer cells by inducing expression of the zinc finger repressor Blimp1 (PRDM1), which then represses ESR1 gene transcription; PRDM1 induction by RelB involves Bcl-2/Ras signaling. siRNA knockdown of RelB; reporter assays for ESR1/PRDM1 promoters; Western blot and RT-PCR in breast cancer cell lines; ChIP; migration assays Molecular and cellular biology Medium 19433448
2010 Human requiem protein (REQ/DPF2) acts as an adaptor molecule linking the NF-κB p52 subunit to the Brm-type SWI/SNF chromatin remodeling complex; REQ and Brm form a larger complex with RelB/p52 upon lymphotoxin stimulation and are recruited to the BLC (CXCL13) promoter; REQ knockdown suppresses anchorage-independent growth of cell lines with constitutively activated noncanonical NF-κB. In vitro binding assays; co-immunoprecipitation; ChIP at BLC promoter; siRNA knockdown of REQ and Brm; reporter assays; soft-agar anchorage-independent growth assay The Journal of biological chemistry Medium 20460684
2011 The paracaspase MALT1 cleaves RelB after Arg-85; RelB cleavage induces its proteasomal degradation and specifically enables DNA binding by RelA- or c-Rel-containing canonical NF-κB complexes; overexpression of uncleaved RelB inhibits canonical NF-κB target gene expression and impairs survival of DLBCL cell lines with constitutive MALT1 activity. In vitro MALT1 cleavage assay; mass spectrometry identification of cleavage site; proteasome inhibitor rescue; RelB overexpression in DLBCL lines; siRNA; reporter assays; EMSA Proceedings of the National Academy of Sciences High 21873235
2012 During dendritic cell activation, RelB functions primarily as a RelB–p50 dimer regulated by canonical IκBs (IκBα and IκBɛ), not as the expected RelB–p52 effector of the noncanonical pathway; IκB control of RelB minimizes spontaneous DC maturation but enables rapid pathogen-responsive maturation; computational modeling predicted that fibroblasts engineered to express DC-like IκB profiles show DC-like RelB control. Genetic mouse models (IκBα-KO, IκBɛ-KO, p52-KO); ChIP; Western blot; computational modeling of NF-κB signaling module; engineered fibroblast DC-like IκB reconstitution Nature immunology High 23086447
2012 LTβR signaling activates the NF-κB2–RelB pathway in adipocyte precursor mesenchymal cells, blocking adipogenesis (suppressing Pparγ and Cebpα expression) and redirecting differentiation toward lymph node stromal cells during embryonic lymph node development. LTβR-KO and NF-κB2/RelB pathway genetic models; in vivo organogenesis assay; transplantation of embryonic adipocyte precursors into newborn lymph nodes; RT-PCR for adipogenic markers Immunity Medium 22940098
2012 Hypercapnia (elevated CO2) induces cleavage of RelB to a lower-molecular-weight form and promotes its nuclear translocation in mouse embryonic fibroblasts and human pulmonary epithelial cells (A549); this processing is sensitive to proteasomal inhibition (MG-132) but independent of GSK3β or MALT1 activity. Western blot for RelB cleavage product; nuclear fractionation; proteasome inhibitor (MG-132); GSK3β inhibitor; MALT1 deficiency; in vivo hypercapnia lung injury model The Journal of biological chemistry Medium 22396550
2014 RelB directly targets the Runx2 promoter to inhibit its activation, thereby negatively regulating osteoblast differentiation and bone formation; RelB-KO mice develop increased trabecular bone mass with age and enhanced osteoblast differentiation associated with increased Runx2. RelB-KO mice; ChIP at Runx2 promoter; reporter assays; in vitro osteoblast differentiation; tibial bone defect transplantation model Journal of bone and mineral research Medium 24115294
2015 An HDAC4–RelB–p52 complex maintains repressive chromatin around proapoptotic genes Bim and BMF in multiple myeloma; disruption of the RelB–HDAC4 interaction (by an HDAC4-mimetic polypeptide) blocks MM growth; RelB–p52 also represses BMF translation by regulating miR-221 expression; RelB is constitutively phosphorylated by ERK1 in MM, and phospho-RelB remains nuclear and is essential for Bim repression. Co-immunoprecipitation (HDAC4–RelB); ChIP at Bim/BMF promoters; HDAC4-mimetic polypeptide disruption; ERK1 kinase assay; siRNA for ERK1; reporter assays; in vivo xenograft growth assay Nature communications High 26455434
2015 RelB/p50 complexes (not p65) directly bind to the YKL-40 promoter in astrocytes and are required for cytokine-driven (IL-1 + oncostatin M) YKL-40 expression; IL-1 promotes RelB/p50 complex formation further enhanced by oncostatin M; dominant-negative IκBα but not p65 depletion inhibits YKL-40. ChIP at YKL-40 promoter; reporter assays with NF-κB site mutagenesis; p65 siRNA vs RelB/p50 manipulation; co-immunoprecipitation of RelB/p50; primary human and mouse astrocytes Journal of immunology Medium 25681350
2016 PAK4 phosphorylates RelB at Ser151, which is critical for RelB–DNA interaction and transcriptional activity; PAK4–RelB–C/EBPβ axis controls senescence-like growth arrest in breast cancer cells; loss of PAK4 increases RELB-driven C/EBPβ expression and triggers senescence. PAK4 kinase assay on RelB; phospho-mutant RelB (S151A); ChIP; siRNA/shRNA knockdown; mammary tumorigenesis in MMTV-PAK4 and MMTV-PyMT mouse models; senescence assays Nature communications High 31399573
2016 Relb acts downstream of SSEA-1+ mTEC stem cells and is necessary for effective production of RANK+ mTEC progenitors; SSEA-1+ mTEC stem cells are present in Relb-KO mice (demonstrating mTEC lineage specification is Relb-independent), but downstream RANK+ progenitor emergence requires Relb. RANK Venus reporter mice; Relb-KO and nude (Foxn1-KO) mice; flow cytometry for RANK/SSEA-1 co-expression; histological analysis of thymus development European journal of immunology Medium 26806881
2017 DeficiencyofRelB in nonhematopoietic stromal cells (extrinsic) rather than cDC intrinsic mechanisms accounts for myeloid expansion and most cDC development defects in Relb-KO mice; cell-intrinsic RelB is required specifically for the Notch2- and LTβR-dependent splenic CD4+ cDC2 subset. Radiation chimeras (wild-type vs Relb-KO bone marrow in Relb-KO vs WT hosts); flow cytometry for DC subsets; conditional analysis Proceedings of the National Academy of Sciences High 28348230
2018 RELB nuclear translocation in cholangiocytes is required for the ductular reaction and biliary fibrosis downstream of CYLD loss; LTβ–RELB axis promotes cholangiocyte proliferation; genetic co-deletion of Relb with Cyld in liver parenchymal cells abolishes ductular reaction, oval cell activation, and biliary fibrosis. Genetic double-KO mice (Cyld/RelbΔLPC); DDC diet model; siRNA knockdown of RELB in human cholangiocytes + LTβR agonist; ChIP; IHC; in situ hybridization Gastroenterology High 30445013
2018 GSK3β modulates RelB degradation via BCL10 phosphorylation; GSK3β inhibition or knockdown reduces MALT1-dependent proteolysis of RelB (and other MALT1 substrates) by diminishing CBM complex formation; this links GSK3β to the control of MALT1-mediated RelB cleavage in T cell activation. GSK3β pharmacologic inhibitors (SB216763, SB415286); siRNA knockdown; Western blot for RelB proteolysis; NF-κB reporter assay; co-immunoprecipitation of CBM complex Scientific reports Medium 29358699
2022 RelB transcriptionally upregulates PD-L1 (CD274) by binding to a proximal NF-κB enhancer element in the CD274 promoter; RelB silencing in prostate cancer cells reduces PD-L1 expression and enhances susceptibility to CD4+/CD8+ T cell killing in vitro and in vivo. ChIP at CD274 promoter; reporter assays with promoter mutagenesis; siRNA/shRNA knockdown of RelB; T cell co-culture cytotoxicity assays; in vivo xenograft and metastasis models Journal of experimental & clinical cancer research Medium 35177112
2023 RelB confers tamoxifen resistance in breast cancer by transcriptionally upregulating GPX4, thereby inhibiting ferroptosis; elevated RelB–GPX4 axis in TAM-resistant cells alleviates TAM-induced ROS accumulation and ferroptotic cell death; suppression of RelB or GPX4 resensitizes resistant cells to tamoxifen in vitro and in vivo. ChIP at GPX4 promoter; reporter assays; siRNA/shRNA knockdown of RelB and GPX4; ferroptosis assays (lipid ROS, cell death markers); in vivo xenograft models Redox biology Medium 37944384

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell 687 7834753
1995 Expression of relB is required for the development of thymic medulla and dendritic cells. Nature 636 7845467
1992 RelB, a new Rel family transcription activator that can interact with p50-NF-kappa B. Molecular and cellular biology 353 1732739
2007 RelB, a new partner of aryl hydrocarbon receptor-mediated transcription. Molecular endocrinology (Baltimore, Md.) 265 17823304
1986 Mechanism of postsegregational killing by the hok gene product of the parB system of plasmid R1 and its homology with the relF gene product of the E. coli relB operon. The EMBO journal 231 3019679
2011 Malt1-dependent RelB cleavage promotes canonical NF-kappaB activation in lymphocytes and lymphoma cell lines. Proceedings of the National Academy of Sciences of the United States of America 190 21873235
2007 Oestrogen signalling inhibits invasive phenotype by repressing RelB and its target BCL2. Nature cell biology 181 17369819
2001 Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines. Journal of immunology (Baltimore, Md. : 1950) 174 11489970
2001 Transcription of the RelB gene is regulated by NF-kappaB. Oncogene 173 11753650
2001 RelB cellular regulation and transcriptional activity are regulated by p100. The Journal of biological chemistry 168 11687592
2003 RelB is required for Peyer's patch development: differential regulation of p52-RelB by lymphotoxin and TNF. The EMBO journal 165 12505990
2012 Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-κB pathways. Nature immunology 156 23086447
2008 A new cross-talk between the aryl hydrocarbon receptor and RelB, a member of the NF-kappaB family. Biochemical pharmacology 154 18955032
2003 Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-kappa B (RelB/p50) in myeloma cells. Oncogene 151 12717418
1997 RelB regulation of chemokine expression modulates local inflammation. The American journal of pathology 142 9250151
1993 Expression of relB transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells. Development (Cambridge, England) 137 8269849
2003 RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100. The Journal of biological chemistry 130 12709443
2003 RelB forms transcriptionally inactive complexes with RelA/p65. The Journal of biological chemistry 126 12657634
2008 RelB is the NF-kappaB subunit downstream of NIK responsible for osteoclast differentiation. Proceedings of the National Academy of Sciences of the United States of America 121 18322009
1997 Nuclear localization of RelB is associated with effective antigen-presenting cell function. Journal of immunology (Baltimore, Md. : 1950) 116 9378953
2012 Lymphotoxin-β receptor signaling through NF-κB2-RelB pathway reprograms adipocyte precursors as lymph node stromal cells. Immunity 112 22940098
2007 Immune modulation and tolerance induction by RelB-silenced dendritic cells through RNA interference. Journal of immunology (Baltimore, Md. : 1950) 112 17442929
2009 RelB and RelE of Escherichia coli form a tight complex that represses transcription via the ribbon-helix-helix motif in RelB. Journal of molecular biology 104 19747491
2003 NIK-dependent RelB activation defines a unique signaling pathway for the development of V alpha 14i NKT cells. The Journal of experimental medicine 96 12810685
2013 Aryl hydrocarbon receptor signaling regulates NF-κB RelB activation during dendritic-cell differentiation. Immunology and cell biology 94 23999131
2008 Daxx represses RelB target promoters via DNA methyltransferase recruitment and DNA hypermethylation. Genes & development 93 18413714
2006 Induction of RelB participates in endotoxin tolerance. Journal of immunology (Baltimore, Md. : 1950) 93 16951372
2003 Direct transcriptional regulation of RelB by 1alpha,25-dihydroxyvitamin D3 and its analogs: physiologic and therapeutic implications for dendritic cell function. The Journal of biological chemistry 91 14507914
2006 IKKalpha controls p52/RelB at the skp2 gene promoter to regulate G1- to S-phase progression. The EMBO journal 84 16902410
2007 Involvement of RelB in aryl hydrocarbon receptor-mediated induction of chemokines. Biochemical and biophysical research communications 81 17900530
2006 RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells. Oncogene 78 16261162
2008 Structural mechanism of transcriptional autorepression of the Escherichia coli RelB/RelE antitoxin/toxin module. Journal of molecular biology 76 18501926
2005 Regulation of relB in dendritic cells by means of modulated association of vitamin D receptor and histone deacetylase 3 with the promoter. Proceedings of the National Academy of Sciences of the United States of America 75 16239345
2005 Opposing roles for RelB and Bcl-3 in regulation of T-box expressed in T cells, GATA-3, and Th effector differentiation. Journal of immunology (Baltimore, Md. : 1950) 74 16081776
2008 NF-kappaB p52, RelB and c-Rel are transported into the nucleus via a subset of importin alpha molecules. Cellular signalling 73 18462924
2009 RelB NF-kappaB represses estrogen receptor alpha expression via induction of the zinc finger protein Blimp1. Molecular and cellular biology 68 19433448
1985 Sequence of the relB transcription unit from Escherichia coli and identification of the relB gene. The EMBO journal 68 2990907
2012 Hodgkin lymphoma requires stabilized NIK and constitutive RelB expression for survival. Blood 67 22968463
2015 The effects of RelB deficiency on lymphocyte development and function. Journal of autoimmunity 66 26385063
2014 NF-κB RelB negatively regulates osteoblast differentiation and bone formation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 64 24115294
1996 Both multiorgan inflammation and myeloid hyperplasia in RelB-deficient mice are T cell dependent. Journal of immunology (Baltimore, Md. : 1950) 64 8892630
2008 NF-kappaB p52:RelB heterodimer recognizes two classes of kappaB sites with two distinct modes. EMBO reports 63 19098713
2001 Signal-specific and phosphorylation-dependent RelB degradation: a potential mechanism of NF-kappaB control. Oncogene 62 11781828
2023 RelB-activated GPX4 inhibits ferroptosis and confers tamoxifen resistance in breast cancer. Redox biology 61 37944384
2008 Stabilization of RelB requires multidomain interactions with p100/p52. The Journal of biological chemistry 61 18321863
2011 Interaction of aryl hydrocarbon receptor and NF-κB subunit RelB in breast cancer is associated with interleukin-8 overexpression. Archives of biochemistry and biophysics 58 21640702
2013 The NF-κB RelB protein is an oncogenic driver of mesenchymal glioma. PloS one 56 23451236
2015 RelB/p50 complexes regulate cytokine-induced YKL-40 expression. Journal of immunology (Baltimore, Md. : 1950) 55 25681350
2004 RelB regulates human dendritic cell subset development by promoting monocyte intermediates. Blood 55 15315978
2015 Transcriptional repression by the HDAC4-RelB-p52 complex regulates multiple myeloma survival and growth. Nature communications 54 26455434
2003 The role of relB in regulating the adaptive immune response. Annals of the New York Academy of Sciences 54 12727647
2019 Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects. International journal of molecular sciences 50 31151139
2010 RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells. Annals of the New York Academy of Sciences 49 20649549
2007 Effector and regulatory T-cell function is differentially regulated by RelB within antigen-presenting cells during GVHD. Blood 48 17327399
2007 Vitamin D receptor-mediated suppression of RelB in antigen presenting cells: a paradigm for ligand-augmented negative transcriptional regulation. Archives of biochemistry and biophysics 48 17367745
2007 Despite inhibition of nuclear localization of NF-kappa B p65, c-Rel, and RelB, 17-beta estradiol up-regulates NF-kappa B signaling in mouse splenocytes: the potential role of Bcl-3. Journal of immunology (Baltimore, Md. : 1950) 48 17641044
1999 Expression of the RelB transcription factor correlates with the activation of human dendritic cells. Immunology 48 10540217
2014 Aryl hydrocarbon receptor (AhR) attenuation of subchronic cigarette smoke-induced pulmonary neutrophilia is associated with retention of nuclear RelB and suppression of intercellular adhesion molecule-1 (ICAM-1). Toxicological sciences : an official journal of the Society of Toxicology 47 24752502
2010 Requiem protein links RelB/p52 and the Brm-type SWI/SNF complex in a noncanonical NF-kappaB pathway. The Journal of biological chemistry 47 20460684
2003 Critical role of RelB serine 368 for dimerization and p100 stabilization. The Journal of biological chemistry 47 12874295
2016 Relb acts downstream of medullary thymic epithelial stem cells and is essential for the emergence of RANK(+) medullary epithelial progenitors. European journal of immunology 46 26806881
2000 RelB nuclear translocation regulates B cell MHC molecule, CD40 expression, and antigen-presenting cell function. Proceedings of the National Academy of Sciences of the United States of America 46 11027342
2013 RelB: an outlier in leukocyte biology. Journal of leukocyte biology 45 23922380
2003 Cyclin E and Bcl-xL cooperatively induce cell cycle progression in c-Rel-/- B cells. Oncogene 45 14627988
2016 B-cell survival and development controlled by the coordination of NF-κB family members RelB and cRel. Blood 44 26773039
2022 The alternative RelB NF-κB subunit is a novel critical player in diffuse large B-cell lymphoma. Blood 43 34232979
2016 Post-Translational Modifications of RelB NF-κB Subunit and Associated Functions. Cells 43 27153093
1997 Thymocytes and RelB-dependent medullary epithelial cells provide growth-promoting and organization signals, respectively, to thymic medullary stromal cells. European journal of immunology 43 9209490
2019 NF-κB/Rel Transcription Factors in Pancreatic Cancer: Focusing on RelA, c-Rel, and RelB. Cancers 42 31277415
2001 Purification of the RelB and RelE proteins of Escherichia coli: RelE binds to RelB and to ribosomes. Journal of bacteriology 42 11274135
2007 CD40 ligand-mediated activation of the de novo RelB NF-kappaB synthesis pathway in transformed B cells promotes rescue from apoptosis. The Journal of biological chemistry 40 17446175
2019 PAK4 suppresses RELB to prevent senescence-like growth arrest in breast cancer. Nature communications 38 31399573
2012 RelB/NF-κB2 regulates corticotropin-releasing hormone in the human placenta. Molecular endocrinology (Baltimore, Md.) 38 22734038
2012 Hypercapnia induces cleavage and nuclear localization of RelB protein, giving insight into CO2 sensing and signaling. The Journal of biological chemistry 37 22396550
2008 RelB sustains IkappaBalpha expression during endotoxin tolerance. Clinical and vaccine immunology : CVI 37 19020113
2022 RelB upregulates PD-L1 and exacerbates prostate cancer immune evasion. Journal of experimental & clinical cancer research : CR 36 35177112
2017 RelB Expression Determines the Differential Effects of Ascorbic Acid in Normal and Cancer Cells. Cancer research 36 28108513
2009 Small interfering RNA targeting RelB protects against renal ischemia-reperfusion injury. Transplantation 36 19424026
2016 Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-κB Transcription Factors RELB and NF-κB2 in B Cells. Journal of immunology (Baltimore, Md. : 1950) 34 26851215
2011 Nuclear factor κB subunits RelB and cRel negatively regulate Toll-like receptor 3-mediated β-interferon production via induction of transcriptional repressor protein YY1. The Journal of biological chemistry 34 22065573
2005 Regulation of RelB expression during the initiation of dendritic cell differentiation. Molecular and cellular biology 34 16107733
1994 Human RelB (I-Rel) functions as a kappa B site-dependent transactivating member of the family of Rel-related proteins. Oncogene 34 8183565
2021 RelB and Neuroinflammation. Cells 32 34198987
2013 RelB/p50 regulates TNF production in LPS-stimulated dendritic cells and macrophages. Cytokine 32 23394901
2013 Frequent engagement of RelB activation is critical for cell survival in multiple myeloma. PloS one 32 23555623
2008 RelB is differentially regulated by IkappaB Kinase-alpha in B cells and mouse lung by cigarette smoke. American journal of respiratory cell and molecular biology 32 18688039
2021 Hypoxia-Inducible Factor 1 Alpha-Mediated RelB/APOBEC3B Down-regulation Allows Hepatitis B Virus Persistence. Hepatology (Baltimore, Md.) 31 33991110
2017 Deficiency of transcription factor RelB perturbs myeloid and DC development by hematopoietic-extrinsic mechanisms. Proceedings of the National Academy of Sciences of the United States of America 31 28348230
2020 17β-Estradiol Promotes Trained Immunity in Females Against Sepsis via Regulating Nucleus Translocation of RelB. Frontiers in immunology 30 32793229
2020 Apigenin Modulates Dendritic Cell Activities and Curbs Inflammation Via RelB Inhibition in the Context of Neuroinflammatory Diseases. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 29 32607691
2005 Induction of the RelB NF-kappaB subunit by the cytomegalovirus IE1 protein is mediated via Jun kinase and c-Jun/Fra-2 AP-1 complexes. Journal of virology 29 15596805
2018 GSK3β modulates NF-κB activation and RelB degradation through site-specific phosphorylation of BCL10. Scientific reports 28 29358699
2007 In vitro selection of optimal RelB/p52 DNA-binding motifs. Biochemical and biophysical research communications 28 17996728
2018 Nuclear Translocation of RELB Is Increased in Diseased Human Liver and Promotes Ductular Reaction and Biliary Fibrosis in Mice. Gastroenterology 27 30445013
2010 Nuclear factor-kappa B family member RelB inhibits human immunodeficiency virus-1 Tat-induced tumor necrosis factor-alpha production. PloS one 27 20686703
2016 RelB/NF-κB links cell cycle transition and apoptosis to endometrioid adenocarcinoma tumorigenesis. Cell death & disease 26 27711077
2013 RelB, together with RelA, sustains cell survival and confers proteasome inhibitor sensitivity of chronic lymphocytic leukemia cells from bone marrow. Journal of molecular medicine (Berlin, Germany) 26 24042463
2008 Differential RelA- and RelB-dependent gene transcription in LTbetaR-stimulated mouse embryonic fibroblasts. BMC genomics 25 19087315
2016 G9a/RelB regulates self-renewal and function of colon-cancer-initiating cells by silencing Let-7b and activating the K-RAS/β-catenin pathway. Nature cell biology 24 27525719
2012 Involvement of DNA binding domain in the cellular stability and importin affinity of NF-κB component RelB. Organic & biomolecular chemistry 24 22395283

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