Affinage

TNFRSF1B

Tumor necrosis factor receptor superfamily member 1B · UniProt P20333

Round 2 corrected
Length
461 aa
Mass
48.3 kDa
Annotated
2026-04-28
130 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TNFRSF1B (TNFR2/p75) is a TNF receptor superfamily member that transduces TNF-α signals to regulate NF-κB activation, JNK signaling, cell survival, and programmed cell death in immune and epithelial cells. The receptor forms pre-ligand trimers via an extracellular PLAD domain, binds TNF-α with lower affinity than TNFR1 (Kd ~4.2 × 10⁻¹⁰ M), and signals by recruiting TRAF2 directly through a cytoplasmic SXXE motif, with TRAF1 and c-IAP1/c-IAP2 assembling indirectly via TRAF2 (PMID:8069916, PMID:8548810, PMID:10206649, PMID:10875917, PMID:9435233). TNFRSF1B potentiates TNFR1-mediated apoptosis and programmed necrosis by triggering c-IAP1-dependent ubiquitination and proteasomal degradation of TRAF2, thereby depleting antiapoptotic signaling capacity (PMID:11907583, PMID:14532286, PMID:9743381). Recurrent gain-of-function mutations in TNFRSF1B, notably Thr377Ile, drive non-canonical NF-κB activation and are found in ~18% of cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome) cases (PMID:26258847).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1990 High

    Molecular cloning of TNFRSF1B established it as a second, distinct TNF receptor with cysteine-rich extracellular repeats that binds both TNF-α and TNF-β, resolving the question of whether multiple TNF receptor species exist.

    Evidence cDNA expression cloning from human fibroblast and serum-derived sequences, radiolabeled ligand binding in transfected cells, and biochemical purification of soluble ectodomains from urine

    PMID:2153136 PMID:2158863 PMID:2160731

    Open questions at the time
    • No intracellular signaling mechanism identified
    • Relative contributions of TNFR1 vs TNFR2 to TNF responses unknown
    • Ectodomain shedding mechanism and regulation uncharacterized
  2. 1990 High

    Demonstration that TNFRSF1B sheds a soluble ectodomain capable of inhibiting TNF revealed a built-in negative regulatory mechanism for the TNF pathway.

    Evidence cDNA expression in COS-7 cells with soluble receptor fragment isolation and TNF-binding assay

    PMID:2172983

    Open questions at the time
    • Identity of the sheddase protease unknown
    • Physiological significance of constitutive shedding not established
  3. 1994 High

    Identification of TRAF1 and TRAF2 as the first signal transducers recruited to the TNFRSF1B cytoplasmic domain answered how a death-domain-lacking receptor signals, establishing that a C-terminal 78-residue region mediates adaptor recruitment.

    Evidence Yeast two-hybrid, biochemical purification, co-immunoprecipitation, and deletion mutagenesis

    PMID:8069916

    Open questions at the time
    • Downstream effectors of TRAF2 at TNFR2 unknown
    • Structural basis of the TRAF2–receptor interaction unresolved
  4. 1995 High

    TRAF2 was established as the direct mediator of NF-κB activation downstream of TNFRSF1B, and c-IAP1/c-IAP2 were identified as TRAF1/TRAF2-dependent components of the receptor signaling complex, defining the core adaptor architecture.

    Evidence Dominant-negative TRAF2 blocking NF-κB reporter activation; biochemical purification and domain mapping of c-IAP1/c-IAP2 interaction with TRAF1/TRAF2

    PMID:7544915 PMID:8548810

    Open questions at the time
    • Enzymatic activity of c-IAPs in TNFR2 signaling not known
    • Mechanism of JNK activation via TRAF2 at TNFR2 not dissected
  5. 1998 High

    The discovery that TNFRSF1B co-stimulation depletes TRAF2 and thereby potentiates TNFR1-induced apoptosis resolved the paradox of how a receptor lacking a death domain enhances cell death, and quantitative binding kinetics explained why TNFR2 preferentially responds to membrane-bound rather than soluble TNF.

    Evidence Dominant-negative and overexpression studies with JNK and cell death readouts; kinetic binding measurements at 37°C showing transient TNFR2–TNF complexes (Kd ~4.2 × 10⁻¹⁰ M)

    PMID:9435233 PMID:9743381

    Open questions at the time
    • Molecular mechanism of TRAF2 depletion (ubiquitination) not yet identified
    • Role of membrane-TNF versus soluble-TNF in vivo not fully delineated
  6. 1999 High

    The crystal structure of the TRAF2 TRAF domain in complex with a TNFR2 peptide revealed the SXXE motif as the TRAF2-binding consensus and showed receptor binding to a shallow surface depression on a trimeric TRAF scaffold, providing the first atomic-level view of TNFRSF1B signal transduction.

    Evidence X-ray crystallography of TRAF2 TRAF-domain/TNFR2-peptide co-crystal

    PMID:10206649

    Open questions at the time
    • Full-length receptor–TRAF2 complex structure lacking
    • Structural basis for selectivity among different TRAF-recruiting receptors not resolved
  7. 2000 High

    Identification of the pre-ligand assembly domain (PLAD) showed that TNFRSF1B forms trimers before ligand binding, revealing that receptor pre-assembly is a prerequisite for TNF-α binding and signaling.

    Evidence Domain mutagenesis, FRET, co-immunoprecipitation, and functional signaling assays

    PMID:10875917

    Open questions at the time
    • Structure of PLAD-mediated trimer interface not determined
    • How ligand binding transitions pre-assembled trimers to active signaling complexes unknown
  8. 2002 High

    The mechanism by which TNFRSF1B potentiates apoptosis was resolved: c-IAP1 functions as an E3 ubiquitin ligase that ubiquitinates TRAF2 for proteasomal degradation upon TNFR2 activation, depleting antiapoptotic signals.

    Evidence In vitro ubiquitination reconstitution, E3-defective c-IAP1 mutant blocking TRAF2 degradation, proteasome inhibitor rescue

    PMID:11907583

    Open questions at the time
    • Ubiquitin chain type on TRAF2 not characterized
    • Whether c-IAP2 has redundant E3 activity in this context not tested
  9. 2003 High

    TNFRSF1B was shown to potentiate TNFR1-dependent programmed necrosis by enhancing RIP kinase recruitment to TNFR1, and TNFR2-deficient mice showed defective antiviral inflammatory responses, linking receptor crosstalk to innate immunity.

    Evidence TNFR2 knockout mice with vaccinia infection, co-immunoprecipitation of RIP with TNFR1 after TNFR2 pre-stimulation

    PMID:14532286

    Open questions at the time
    • Whether TNFR2 directly modulates RIP phosphorylation status unknown
    • Necroptotic pathway components downstream of RIP in this context not mapped
  10. 2011 High

    Progranulin was identified as an alternative endogenous ligand that competes with TNF-α for binding to TNFRSF1B, expanding the receptor's ligand repertoire and establishing a new anti-inflammatory axis.

    Evidence Direct binding assays, competitive displacement of TNF-α, progranulin-deficient mice with inflammatory arthritis, therapeutic rescue with engineered Atsttrin fragment

    PMID:21393509

    Open questions at the time
    • Binding site overlap between progranulin and TNF-α on TNFR2 not structurally resolved
    • Whether progranulin activates or only blocks TNFR2 signaling remains debated
  11. 2015 High

    Recurrent somatic TNFRSF1B mutations, especially Thr377Ile, were identified as oncogenic drivers in cutaneous T-cell lymphoma, demonstrating that gain-of-function TNFR2 signaling activates non-canonical NF-κB and is targetable with proteasome inhibition.

    Evidence Whole-genome sequencing of mycosis fungoides/Sézary syndrome, functional expression of Thr377Ile mutant in T cells, NF-κB signaling and bortezomib sensitivity assays

    PMID:26258847

    Open questions at the time
    • Structural mechanism by which Thr377Ile activates non-canonical NF-κB not determined
    • Whether wild-type TNFR2 also engages non-canonical NF-κB under physiological conditions unclear
    • Clinical efficacy of proteasome inhibitors in TNFRSF1B-mutant lymphoma not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length structure of the TNFR2 signaling complex, the precise mechanism of PLAD-mediated pre-assembly transition to active signaling, whether TNFR2-selective agonism versus antagonism can be therapeutically harnessed, and the contribution of non-canonical NF-κB signaling through wild-type TNFR2 in normal immune homeostasis.
  • No full-length TNFR2 signaling complex structure available
  • Therapeutic TNFR2-selective agents not clinically validated
  • Physiological role of non-canonical NF-κB through wild-type TNFR2 not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 3
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1643685 Disease 1
Partners
BIRC2BIRC3GRNKRT18KRT8RIPK1TRAF1TRAF2
Complex memberships
TNFR2–TRAF1–TRAF2–cIAP1/2 signaling complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 Molecular cloning of TNFRSF1B (TNFR2/p75 TNF receptor): a cDNA encoding a 461-amino acid integral membrane protein was isolated from a human lung fibroblast library by direct expression screening with radiolabeled TNF-alpha. The extracellular domain contains cysteine-rich repeats homologous to the nerve growth factor receptor, defining a receptor superfamily. cDNA expression cloning, radiolabeled ligand binding, sequence analysis Science High 2160731
1990 TNFRSF1B was independently cloned as a 415-amino acid TNF receptor; the extracellular cysteine-rich domain is homologous to the NGF receptor and Bp50. Cells transfected with TNFR expression vector specifically bind both TNF-alpha and TNF-beta with equal affinity. cDNA cloning from serum TNF-binding protein sequences, transfection, radiolabeled ligand binding Cell High 2158863
1990 Two distinct soluble TNF-binding proteins (corresponding to shed ectodomains of TNFR1 and TNFR2) were purified from human urine; antibodies against each inhibit TNF binding to cells from different cell lines with varying efficacy, establishing that two distinct receptor species exist on cell surfaces. Ligand-affinity purification, NH2-terminal sequencing, antibody blocking of cell-surface TNF binding The Journal of biological chemistry High 2153136
1990 TNFRSF1B (TNFrII) can shed a naturally occurring soluble TNF inhibitor through proteolytic cleavage of its ectodomain; expression of the TNFrII cDNA in COS-7 cells produced a receptor that binds TNF-alpha and releases a soluble inhibitory fragment. cDNA expression in COS-7 cells, TNF-binding assay, protein isolation from U-937 cells Proceedings of the National Academy of Sciences of the United States of America High 2172983
1994 TRAF1 and TRAF2 were identified as the first signal transducers that associate with the cytoplasmic domain of TNFRSF1B (TNF-R2). A C-terminal 78-amino acid region of the TNF-R2 cytoplasmic domain is required for signal transduction and mediates this interaction. TRAF1 and TRAF2 form homo- and heterotypic dimers, with TRAF2 contacting the receptor directly and TRAF1 associating indirectly through TRAF2. Yeast two-hybrid, biochemical purification, co-immunoprecipitation, mutational analysis Cell High 8069916
1995 TRAF2-mediated activation of NF-κB is a key signaling output of TNFRSF1B (TNF-R2): overexpression of TRAF2 was sufficient to induce NF-κB activation, and a dominant-negative TRAF2 lacking the N-terminal RING finger domain blocked NF-κB activation by TNF-R2 and CD40. Transient transfection, NF-κB reporter assays, dominant-negative mutant analysis Science High 7544915
1995 The TNFRSF1B (TNFR2) signaling complex contains c-IAP1 and c-IAP2, two novel mammalian members of the inhibitor of apoptosis (IAP) family. These proteins do not contact TNFR2 directly but associate with TRAF1 and TRAF2 through their N-terminal BIR motif-comprising domain, requiring a TRAF2-TRAF1 heterocomplex for recruitment. Biochemical purification, molecular cloning, co-immunoprecipitation, interaction domain mapping Cell High 8548810
1995 Both TNFR60 (TNFR1) and TNFR80 (TNFRSF1B/TNFR2) are involved in signaling endothelial tissue factor expression by juxtacrine (membrane-bound) TNF-alpha. Selective triggering of either receptor with agonistic antibodies induced tissue factor expression, and simultaneous blockade of both was required for full inhibition. Antagonistic and agonistic antibody blocking, HUVECs co-culture with membrane TNF-expressing CHO transfectants, tissue factor assay Blood Medium 7544644
1996 TNFRSF1B (TNF-R2/p75) signaling is required for the migration of Langerhans cells from skin to draining lymph nodes. In TNF-R1-deficient mice, anti-TNF-alpha antibody still inhibited Langerhans cell accumulation in lymph nodes following hapten application, implicating TNF-R2 as the mediator of this migratory response. TNF-R1 gene-targeted mice, hapten (FITC) application, flow cytometry, neutralizing antibody studies Immunology Medium 8690462
1996 Distinct domains of TRAF2 mediate different functions in TNFRSF1B signaling: the N-terminal RING finger and two adjacent zinc fingers are required for NF-κB activation; the TRAF-N and TRAF-C subdomains independently mediate self-association and TRAF1 interaction; interaction with TNF-R2 requires C-terminal sequences of TRAF-C; interaction with RIP occurs via N-terminal TRAF-C sequences. Extensive mutational analysis (point mutants and chimeric proteins), NF-κB reporter assays, co-immunoprecipitation The Journal of biological chemistry High 8702708
1997 Constitutive shedding of both p55 (TNFR1) and p75 (TNFRSF1B/TNFR2) murine TNF receptors occurs in vivo; administration of TNF receptor-specific mAbs to normal mice caused linear accumulation of soluble receptor in circulation by blocking clearance of constitutively shed receptor. Accumulated soluble receptor was capable of inhibiting TNF-induced responses in vivo. In vivo mAb administration to normal mice, soluble receptor ELISA, TNF-induced response assays Journal of immunology Medium 9103455
1998 TNFRSF1B (TNFR80)-mediated enhancement of TNFR60-induced cell death is TNFR60-selective and is mediated through TRAF2: TNFR80 costimulation abrogates antiapoptotic TRAF2-dependent signaling from TNFR60 by negatively regulating TRAF2 function, thereby potentiating TNF-induced cell death. This was confirmed by showing that TNFR80 prestimulation reduced TNFR60-induced JNK activation. TRAF2 overexpression and dominant-negative mutant transfection in HeLa cells, cell death assays, JNK activation assays Journal of immunology High 9743381
1998 TNF-alpha-induced apoptosis of CD8+ T cells is mediated by macrophages through membrane-bound TNF (mbTNF) interacting with TNFRSF1B (TNFRII) on CD8+ T cells. HIV gp120 interaction with CXCR4 upregulates both mbTNF on macrophages and TNFRII on CD8+ T cells, and TNFRII-blocking antibodies prevent this apoptosis. Blocking antibodies against TNFRII, HIV infection of PBMCs, flow cytometry, apoptosis assays Nature Medium 9744279
1998 TNF-R1 (CD120a) is the high-affinity receptor for soluble TNF (Kd = 1.9 × 10⁻¹¹ M at 37°C) while TNFRSF1B/TNF-R2 has significantly lower affinity for soluble TNF (Kd = 4.2 × 10⁻¹⁰ M). The high affinity of TNF-R1 derives from marked stability of ligand-receptor complexes, whereas TNF-R2 forms only transient interactions with soluble TNF, explaining the predominant role of TNF-R1 in responses to soluble TNF. Kinetic binding measurements (association/dissociation rate constants) at 37°C, Scatchard analysis Proceedings of the National Academy of Sciences of the United States of America High 9435233
1999 Crystal structure of the TRAF domain of human TRAF2 reveals a trimeric self-association and, in complex with a TNF-R2 peptide, shows the receptor peptide binding to a conserved shallow surface depression on one TRAF-C domain. An SXXE motif serves as a TRAF2-binding consensus sequence in TNFRSF1B. X-ray crystallography, solution studies confirming trimeric state, peptide-protein co-crystal structure Nature High 10206649
2000 A pre-ligand-binding assembly domain (PLAD) in the extracellular region of TNFRSF1B (TNFR2/p80) mediates specific ligand-independent assembly of receptor trimers. The PLAD is physically distinct from the ligand-binding domain but is necessary and sufficient for TNFR complex assembly and TNF-alpha binding and signaling. Domain mapping by mutagenesis, FRET, co-immunoprecipitation, functional signaling assays Science High 10875917
2000 Keratin 8 and keratin 18 bind the cytoplasmic domain of TNFRSF1B (TNFR2/CD120b) and moderate TNF-induced JNK signaling and NF-κB activation. K8/K18-deficient epithelial cells are ~100× more sensitive to TNF-induced death, demonstrating that keratins modulate TNFR2 intracellular signaling. K8/K18 knockout mice, direct binding assays, JNK and NF-κB signaling assays, in vivo concanavalin A hepatotoxicity model The Journal of cell biology High 10747083
2002 TNF-RII (TNFRSF1B) activation induces ubiquitination and proteasomal degradation of TRAF2 through c-IAP1, which acts as an E3 ubiquitin ligase. c-IAP1 bound TRAF2 and ubiquitinated it specifically; E3-defective c-IAP1 prevented TNF-alpha-induced TRAF2 degradation and inhibited apoptosis. This defines a mechanism by which TNFRSF1B potentiates TNF-induced apoptosis by depleting antiapoptotic TRAF2. In vitro ubiquitination assay, E3-defective mutant expression, proteasome inhibitor studies, co-immunoprecipitation Nature High 11907583
2003 TNFRSF1B (TNFR-2) signaling potentiates programmed necrosis via TNFR-1 through recruitment of RIP kinase to the TNFR-1 complex. Pre-stimulation through TNFR-2 enhanced TNF-induced cell death and RIP recruitment to TNFR-1. TNFR-2-deficient mice showed reduced liver inflammation and defective viral clearance during vaccinia virus infection, linking TNFRSF1B to antiviral responses. TNFR-2 knockout mice, viral infection model, co-immunoprecipitation of RIP with TNFR-1, death effector domain protein expression studies The Journal of biological chemistry High 14532286
2004 A physical and functional map of the TNF-alpha/NF-κB signaling pathway identified 221 molecular associations and 80 previously unknown interactors around 32 known pathway components including TNFRSF1B, using tandem affinity purification and mass spectrometry, validated by RNAi functional studies. Tandem affinity purification (TAP), LC-MS/MS, RNAi functional validation, network analysis Nature cell biology High 14743216
2011 Progranulin (PGRN) binds directly to TNFRSF1B (TNFR2) and TNFR1, competing with TNF-alpha for receptor binding. Atsttrin, an engineered PGRN fragment, selectively binds TNFRs and inhibits TNF-alpha-activated intracellular signaling. PGRN-deficient mice were susceptible to inflammatory arthritis, and PGRN/Atsttrin treatment reversed disease in multiple arthritis models. Direct binding assays, competitive displacement, PGRN-deficient mice, multiple arthritis mouse models, intracellular signaling assays Science High 21393509
2015 Recurrent point mutations and genomic gains of TNFRSF1B (encoding TNFR2) occur in 18% of mycosis fungoides and Sézary syndrome patients. The recurrent TNFR2 Thr377Ile mutant expressed in T cells leads to enhanced non-canonical NF-κB signaling that is sensitive to proteasome inhibitor bortezomib, establishing TNFRSF1B as an oncogenic driver in cutaneous T cell lymphoma. Whole-genome sequencing, targeted sequencing, functional expression of mutant TNFR2 in T cells, NF-κB signaling assays, bortezomib sensitivity assays Nature genetics High 26258847
2019 miR-125a-5p directly targets TNFRSF1B mRNA: luciferase reporter assay confirmed TNFRSF1B as the target gene of miR-125a-5p. Upregulation of miR-125a-5p inhibited TNFRSF1B protein expression and promoted osteoclast differentiation, while downregulation had opposite effects, establishing TNFRSF1B as a suppressor of osteoclastogenesis regulated by miR-125a-5p. Dual luciferase reporter assay, miRNA mimic/inhibitor transfection, western blot, osteoclast differentiation assay Cellular & molecular biology letters Medium 30976285
2021 LncRNA NEAT1 stabilizes TNFRSF1B mRNA through direct RNA-protein interaction (co-precipitated TNFRSF1B mRNA in RNA pulldown assay) and promotes NF-κB p65 nuclear translocation and intestinal inflammation. Knockdown of NEAT1 reduced TNFRSF1B expression and NF-κB activation; overexpression of TNFRSF1B rescued these effects. RNA pulldown, RNA decay assay, siRNA knockdown, western blot, NF-κB p65 immunofluorescence, ELISA of inflammatory cytokines, DSS colitis mouse model Annals of translational medicine Medium 34268386
2021 Proteome-scale affinity-purification mass spectrometry (BioPlex 3.0) identified interaction partners of TNFRSF1B in 293T and HCT116 cells, contributing to a cell-line-specific interactome network. Cell-specific interactions of TNFRSF1B link core complexes to other subnetworks, revealing rewiring of the receptor's interaction landscape across cell types. Affinity-purification mass spectrometry (AP-MS), reciprocal validation, proteome-scale network analysis across two cell lines Cell Medium 33961781

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1990 Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell 1077 2158863
1990 A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science (New York, N.Y.) 1053 2160731
1995 The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell 1046 8548810
1994 A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell 939 8069916
1995 TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40. Science (New York, N.Y.) 938 7544915
1995 The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell 885 7859281
2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nature cell biology 841 14743216
1995 p75 and Trk: a two-receptor system. Trends in neurosciences 722 7571013
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2000 A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science (New York, N.Y.) 662 10875917
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2010 Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford, England) 652 20194223
2011 The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science (New York, N.Y.) 620 21393509
2002 Neurotrophin signaling through the p75 neurotrophin receptor. Progress in neurobiology 582 12169297
1990 Two tumor necrosis factor-binding proteins purified from human urine. Evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors. The Journal of biological chemistry 572 2153136
2014 Tumor necrosis factor alpha: a link between neuroinflammation and excitotoxicity. Mediators of inflammation 560 24966471
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1998 Competitive signaling between TrkA and p75 nerve growth factor receptors determines cell survival. The Journal of neuroscience : the official journal of the Society for Neuroscience 401 9547236
1994 The p75 neurotrophin receptor. Journal of neurobiology 395 7852992
2002 TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature 389 11907583
2002 A p75(NTR) and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein. Nature neuroscience 374 12426574
2003 A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses. The Journal of biological chemistry 372 14532286
1998 The type 1 receptor (CD120a) is the high-affinity receptor for soluble tumor necrosis factor. Proceedings of the National Academy of Sciences of the United States of America 360 9435233
2002 ProNGF induces p75-mediated death of oligodendrocytes following spinal cord injury. Neuron 358 12408842
1998 Apoptosis of CD8+ T cells is mediated by macrophages through interaction of HIV gp120 with chemokine receptor CXCR4. Nature 340 9744279
2002 The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho. The Journal of cell biology 325 12011108
1990 A second tumor necrosis factor receptor gene product can shed a naturally occurring tumor necrosis factor inhibitor. Proceedings of the National Academy of Sciences of the United States of America 323 2172983
1999 Structural basis for self-association and receptor recognition of human TRAF2. Nature 305 10206649
1995 Expression and functional significance of tumor necrosis factor receptors in human myocardium. Circulation 296 7664431
1999 Neurotrophin signaling via Trks and p75. Experimental cell research 287 10579918
1995 Early events in neurotrophin signalling via Trk and p75 receptors. Current opinion in neurobiology 278 8580709
1996 Anatomy of TRAF2. Distinct domains for nuclear factor-kappaB activation and association with tumor necrosis factor signaling proteins. The Journal of biological chemistry 276 8702708
1997 Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1. The Journal of biological chemistry 256 9162022
2000 Keratin-dependent, epithelial resistance to tumor necrosis factor-induced apoptosis. The Journal of cell biology 229 10747083
2002 Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system. The Journal of clinical endocrinology and metabolism 227 12364441
2015 Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2. Nature genetics 224 26258847
2007 Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. The Journal of infectious diseases 223 17703412
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
1999 Association of the p75 neurotrophin receptor with TRAF6. The Journal of biological chemistry 205 9915784
2000 The p75 neurotrophin receptor and neuronal apoptosis. Progress in neurobiology 188 10704998
2008 The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication. PLoS pathogens 187 18369482
1999 p75 neurotrophin receptor expression is induced in apoptotic neurons after seizure. The Journal of neuroscience : the official journal of the Society for Neuroscience 182 10436046
2005 The interaction of LEDGF/p75 with integrase is lentivirus-specific and promotes DNA binding. The Journal of biological chemistry 170 15749713
2012 LEDGF (p75) promotes DNA-end resection and homologous recombination. Nature structural & molecular biology 156 22773103
2000 p75 is important for axon growth and schwann cell migration during development. The Journal of neuroscience : the official journal of the Society for Neuroscience 143 11027232
2015 The p75 neurotrophin receptor: at the crossroad of neural repair and death. Neural regeneration research 138 26109945
2007 The p75 neurotrophin receptor is a central regulator of glioma invasion. PLoS biology 138 17696644
1999 Caveolin interacts with Trk A and p75(NTR) and regulates neurotrophin signaling pathways. The Journal of biological chemistry 137 9867838
2004 The p75 neurotrophin receptor: multiple interactors and numerous functions. Progress in brain research 132 14699954
2007 p75 neurotrophin receptor expression defines a population of BDNF-responsive neurogenic precursor cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 131 17494700
2007 The p75 neurotrophin receptor. The international journal of biochemistry & cell biology 126 17681869
1999 Engagement of p75/AIRM1 or CD33 inhibits the proliferation of normal or leukemic myeloid cells. Proceedings of the National Academy of Sciences of the United States of America 122 10611343
2009 Activation of the p75 neurotrophin receptor through conformational rearrangement of disulphide-linked receptor dimers. Neuron 121 19376068
1998 TNFR80-dependent enhancement of TNFR60-induced cell death is mediated by TNFR-associated factor 2 and is specific for TNFR60. Journal of immunology (Baltimore, Md. : 1950) 114 9743381
2008 Integrase, LEDGF/p75 and HIV replication. Cellular and molecular life sciences : CMLS 112 18264802
2003 PKA phosphorylates the p75 receptor and regulates its localization to lipid rafts. The EMBO journal 106 12682012
2006 Transcriptional co-activator p75 binds and tethers the Myc-interacting protein JPO2 to chromatin. Journal of cell science 102 16735438
1999 p75 neurotrophin receptor as a modulator of survival and death decisions. Microscopy research and technique 94 10383114
2014 Role of p75 neurotrophin receptor in stem cell biology: more than just a marker. Cellular and molecular life sciences : CMLS 92 24481864
2014 The biological functions and signaling mechanisms of the p75 neurotrophin receptor. Handbook of experimental pharmacology 89 24668472
2001 Characterization of a p75(NTR) apoptotic signaling pathway using a novel cellular model. The Journal of biological chemistry 88 11451944
2006 Retroviral DNA integration: HIV and the role of LEDGF/p75. Trends in genetics : TIG 87 16730094
2002 IL-12: the role of p40 versus p75. Scandinavian journal of immunology 86 12100467
2005 The p75 neurotrophin receptor in human development and disease. Progress in neurobiology 82 16297524
2014 Dynamic nature of the p75 neurotrophin receptor in response to injury and disease. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 81 25239528
1996 Tumour necrosis factor receptor II (p75) signalling is required for the migration of Langerhans' cells. Immunology 78 8690462
2002 The p75 neurotrophin receptor interacts with multiple MAGE proteins. The Journal of biological chemistry 76 12414813
2002 Dual role for p75(NTR) signaling in survival and cell death: can intracellular mediators provide an explanation? Journal of neuroscience research 75 11992464
2008 The p75 neurotrophin receptor regulates hippocampal neurogenesis and related behaviours. The European journal of neuroscience 72 18717734
1996 High levels of sTNFR p75 and TNF alpha in dengue-infected patients. Microbiology and immunology 72 8887351
1995 TrkA, TrkB and p75 mRNA expression is developmentally regulated in the rat retina. Brain research 72 8750972
2009 Multiple roles of the p75 neurotrophin receptor in the nervous system. The Journal of international medical research 70 19383220
2004 Multi-tasking by the p75 neurotrophin receptor: sortilin things out? EMBO reports 69 15470383
2015 Structural basis of death domain signaling in the p75 neurotrophin receptor. eLife 68 26646181
2022 NGF-p75 signaling coordinates skeletal cell migration during bone repair. Science advances 65 35302859
2019 MiR-125a-5p promotes osteoclastogenesis by targeting TNFRSF1B. Cellular & molecular biology letters 64 30976285
1998 Soluble tumor necrosis factor receptor (p75) fusion protein (ENBREL) as a therapy for rheumatoid arthritis. Rheumatic diseases clinics of North America 63 9710888
2004 Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor. Journal of cell science 62 15507485
1997 Modulation of nerve growth factor internalization by direct interaction between p75 and TrkA receptors. Journal of neuroscience research 61 9379485
2022 High-affinity TrkA and p75 neurotrophin receptor complexes: A twisted affair. The Journal of biological chemistry 59 35051416
2007 p75 neurotrophin receptor inhibits invasion and metastasis of gastric cancer. Molecular cancer research : MCR 57 17510309
1995 Both tumor necrosis factor receptors, TNFR60 and TNFR80, are involved in signaling endothelial tissue factor expression by juxtacrine tumor necrosis factor alpha. Blood 57 7544644
2001 Tumor necrosis factor receptor 2 gene (TNFRSF1B) in genetic basis of coronary artery disease. Journal of molecular medicine (Berlin, Germany) 55 11357933
2010 A novel hypothesis for Alzheimer disease based on neuronal tetraploidy induced by p75 (NTR). Cell cycle (Georgetown, Tex.) 53 20436277
2004 Ternary complex with Trk, p75, and an ankyrin-rich membrane spanning protein. Journal of neuroscience research 53 15378608
2013 Role of TNFRSF1B polymorphisms in the response of Crohn's disease patients to infliximab. Human immunology 52 24121042
2000 Identification of TNFRSF1B as a novel modifier gene in familial combined hyperlipidemia. Human molecular genetics 50 10958645
1998 Coupling of the p75 neurotrophin receptor to sphingolipid signaling. Annals of the New York Academy of Sciences 49 9668341
2000 p75 neurotrophin receptor signaling: mechanisms for neurotrophic modulation of cell stress? Journal of neuroscience research 48 10900070
2015 Glioma invasion mediated by the p75 neurotrophin receptor (p75(NTR)/CD271) requires regulated interaction with PDLIM1. Oncogene 47 26119933
1997 Constitutive shedding of both p55 and p75 murine TNF receptors in vivo. Journal of immunology (Baltimore, Md. : 1950) 47 9103455
2019 Neurotrophin receptor p75 mediates amyloid β-induced tau pathology. Neurobiology of disease 46 31394202
2012 p75 neurotrophin receptor regulates glucose homeostasis and insulin sensitivity. Proceedings of the National Academy of Sciences of the United States of America 46 22460790
2017 Neurotrophin Receptors TrkA, p75NTR, and Sortilin Are Increased and Targetable in Thyroid Cancer. The American journal of pathology 45 29037860
2003 Expression of NGF, Trka and p75 in human cartilage. European journal of histochemistry : EJH 44 14706929
2011 The p75 receptor mediates axon growth inhibition through an association with PIR-B. Cell death & disease 43 21881600
1999 Clinical experience with soluble TNF p75 receptor in rheumatoid arthritis. Seminars in arthritis and rheumatism 42 10622681
1996 TRK and p75 neurotrophin receptor systems in the developing human brain. The Journal of comparative neurology 42 8761930
2001 Expression and function of Xenopus laevis p75(NTR) suggest evolution of developmental regulatory mechanisms. Journal of neurobiology 41 11598917
2004 The p75 neurotrophin receptor enhances TrkA signalling by binding to Shc and augmenting its phosphorylation. Journal of neurochemistry 39 15056278
2002 Linkage disequilibrium between polymorphisms in the human TNFRSF1B gene and their association with bone mass in perimenopausal women. Human molecular genetics 37 12217957
2014 Polarized expression of p75(NTR) specifies axons during development and adult neurogenesis. Cell reports 35 24685135
2013 Involvement of NT3 and P75(NTR) in photoreceptor degeneration following selective Müller cell ablation. Journal of neuroinflammation 35 24224958
2004 A functional interaction between the p75 neurotrophin receptor interacting factors, TRAF6 and NRIF. The Journal of biological chemistry 35 14960584
2021 LncRNA NEAT1 mediates intestinal inflammation by regulating TNFRSF1B. Annals of translational medicine 34 34268386
2019 P40 and P75 Are Singular Functional Muramidases Present in the Lactobacillus casei /paracasei/rhamnosus Taxon. Frontiers in microbiology 34 31297099
2019 The p75 Neurotrophin Receptor Facilitates TrkB Signaling and Function in Rat Hippocampal Neurons. Frontiers in cellular neuroscience 34 31736712
2008 Small molecule modulation of p75 neurotrophin receptor functions. CNS & neurological disorders drug targets 34 18289033
2004 From cell death to neuronal regeneration, effects of the p75 neurotrophin receptor depend on interactions with partner subunits. Science's STKE : signal transduction knowledge environment 34 15173600
2018 Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase-dependent phosphorylation. Proceedings of the National Academy of Sciences of the United States of America 33 29997176
2002 Control of the cell cycle by neurotrophins: lessons from the p75 neurotrophin receptor. Histology and histopathology 33 12371150
2004 The role of neurotransmission and the Chopper domain in p75 neurotrophin receptor death signaling. Progress in brain research 32 14699955
2003 Functional inhibition of the p75 receptor using a small interfering RNA. Biochemical and biophysical research communications 32 12565852
2005 No association with hypertension of CLCNKB and TNFRSF1B polymorphisms at a hypertension locus on chromosome 1p36. Journal of hypertension 31 16003175
2005 The expression of p75 neurotrophin receptor protects against the neurotoxicity of soluble oligomers of beta-amyloid. Experimental cell research 31 16223482
2018 Swedish Nerve Growth Factor Mutation (NGFR100W) Defines a Role for TrkA and p75NTR in Nociception. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 29483280
2015 SORT1 Mutation Resulting in Sortilin Deficiency and p75(NTR) Upregulation in a Family With Essential Tremor. ASN neuro 30 26297037
2011 Inhibitors of the interactions between HIV-1 IN and the cofactor LEDGF/p75. ChemMedChem 30 21506277
2009 Signaling of the neurotrophin receptor p75 in relation to Alzheimer's disease. Biochemical and biophysical research communications 30 19818333
2016 Structural Basis of p75 Transmembrane Domain Dimerization. The Journal of biological chemistry 29 27056327
2006 GDNF gene delivery via the p75(NTR) receptor rescues injured motor neurons. Experimental neurology 29 16842780
2009 Virological and cellular roles of the transcriptional coactivator LEDGF/p75. Current topics in microbiology and immunology 28 20012527
2016 Structural Characterization of the p75 Neurotrophin Receptor: A Stranger in the TNFR Superfamily. Vitamins and hormones 27 28215307
2009 Cigarette smoking, STAT4 and TNFRSF1B polymorphisms, and systemic lupus erythematosus in a Japanese population. The Journal of rheumatology 27 19684152
2006 Functional monoclonal antibodies to p75 neurotrophin receptor raised in knockout mice. Journal of neuroscience methods 27 16828166
2017 p75NTR antagonists attenuate photoreceptor cell loss in murine models of retinitis pigmentosa. Cell death & disease 26 28703796
2008 Regulation of cardiac innervation and function via the p75 neurotrophin receptor. Autonomic neuroscience : basic & clinical 26 18430612
2017 p75 neurotrophin receptor interacts with and promotes BACE1 localization in endosomes aggravating amyloidogenesis. Journal of neurochemistry 25 28869759
2004 Upregulation and colocalization of p75 and Nav1.8 in Purkinje neurons in experimental autoimmune encephalomyelitis. Neuroscience letters 25 15464262