Affinage

MIF

Anti-Muellerian hormone · UniProt P03971

Length
560 aa
Mass
59.2 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 25 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

MIF is a constitutively expressed, secreted ~12.5 kDa cytokine that drives inflammation, leukocyte recruitment, and cell proliferation/survival by signaling extracellularly through the high-affinity receptor CD74 (Kd ~9 nM), which is required for MIF-induced ERK1/2 activation, proliferation, and PGE2 production (PMID:12782713, PMID:7947826). At the cell surface CD74 assembles with co-receptors to form functional signaling complexes: CD74/CXCR4 heterocomplexes mediate MIF-specific AKT activation and leukocyte/CD4+ T-cell migration (PMID:19665027, PMID:38992165), while MIF recruits CD44 into a CD74/CD44 complex that drives MAPK and RhoA signaling and an invasive phenotype (PMID:27872288). Through these receptor complexes MIF activates ERK1/2, p38, AKT, and RhoA in diverse cell types—podocytes, macrophages, microglia, and fibroblasts—to control chemokine output (e.g., MIP-2), TRAIL/MCP-1 induction, macrophage polarization, and adhesion-dependent cyclin D1 expression and DNA synthesis (PMID:19413900, PMID:18842989, PMID:27157615, PMID:12297513). MIF also functions independently of CD74 as an autocrine growth factor, suppressing the Rb/E2F and p53 tumor-suppressor axes: loss of MIF (together with its homolog D-DT) restores p53 phosphorylation and activity via ROS-driven AMPK activation, and MIF loss delays Myc-induced lymphomagenesis by perturbing E2F and enhancing p53 function (PMID:12297513, PMID:24932684, PMID:15947793). Intracellularly, MIF acts as a 3' flap nuclease that translocates to the nucleus in S phase and co-localizes with PARP1 at replication forks to resolve replication stress, with nuclease-dead MIF failing to rescue DNA synthesis defects (PMID:34012010). MIF activity is set by post-translational modification: HDAC6 deacetylates MIF at K78 to permit MIF–AIF interaction and nuclear translocation in ischemic neurons (PMID:35585040), and C-terminal O-GlcNAcylation directs a secreted MIF pool that binds EGFR to antagonize EGF signaling (PMID:26280537). MIF additionally binds PINK1 to block PINK1–Parkin coupling and mitophagy (PMID:38956064) and is the first identified endogenous inhibitor of the serine protease HTRA1 (PMID:28726057). MIF transcription is controlled by ICBP90/UHRF1 acting at the polymorphic −794 CATT microsatellite (PMID:26752645), by HIF-1α through a hypoxia response element (PMID:16854377), and by the nuclear receptor RORα (PMID:27925372).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 High

    Established MIF as a defined, bioactive protein rather than a crude activity, anchoring all subsequent mechanism: recombinant MIF is a 12.5 kDa, structured protein with intrinsic immunoregulatory function.

    Evidence Recombinant human/mouse MIF expression, mass spectrometry, circular dichroism, and bioactivity assays (migration inhibition, TNF-α, nitric oxide)

    PMID:7947826

    Open questions at the time
    • No receptor or signaling mechanism identified
    • Secretion route and structural basis of activity not defined
  2. 2002 Medium

    Showed MIF is a secreted autocrine mediator of growth signaling, linking it to cell-cycle control via the Rb/E2F axis before its receptor was known.

    Evidence MIF-null mouse fibroblasts with recombinant reconstitution, PKC inhibition, cyclin D1 reporter, Rb/E2F activity assays

    PMID:12297513

    Open questions at the time
    • Receptor mediating autocrine MIF action not identified here
    • Mechanism connecting secreted MIF to Rb/E2F not resolved
  3. 2003 High

    Identified the high-affinity MIF receptor, converting MIF from an orphan cytokine into a defined receptor-ligand signaling system.

    Evidence Expression cloning, surface plasmon resonance binding (Kd ~9 nM), and CD74-dependent ERK1/2 / proliferation / PGE2 assays

    PMID:12782713

    Open questions at the time
    • CD74 lacks an intracellular signaling domain — co-receptor requirement unaddressed
    • Quantitative contribution of CD74 vs other binding partners not resolved
  4. 2005 Medium

    Demonstrated in vivo that MIF promotes tumorigenesis through tumor-suppressor circuits, establishing the E2F/p53 axis as a key MIF effector pathway.

    Evidence Eμ-Myc lymphoma model on MIF-null background, E2F DNA-binding and p53 pathway assays, tumor onset kinetics

    PMID:15947793

    Open questions at the time
    • Molecular link between MIF and E2F/p53 regulation not mechanistically defined
    • Does not distinguish secreted vs intracellular MIF activity
  5. 2006 Medium

    Defined transcriptional control of MIF under hypoxia, explaining inducible MIF expression in low-oxygen tissue contexts.

    Evidence HIF-1α overexpression, HRE reporter and promoter deletion assays, CREB modulation

    PMID:16854377

    Open questions at the time
    • Relative contribution of HIF-1α vs other promoter elements in vivo not quantified
  6. 2009 Medium

    Resolved the co-receptor problem by showing CD74 partners with CXCR4 (and engages p44/p42 MAPK in macrophages), explaining how the signaling-incompetent CD74 transduces MIF signals to AKT and chemokine output.

    Evidence Co-IP of endogenous CD74/CXCR4, AMD3100/antibody blockade, AKT phosphorylation, and in vivo MIF-induced alveolar neutrophil/MIP-2 assays

    PMID:19413900 PMID:19665027 PMID:19726058

    Open questions at the time
    • Stoichiometry of the CD74/CXCR4 complex not defined
    • Autocrine MIF growth role in pancreatic cancer rests on single-method knockdown
  7. 2014 Medium

    Showed MIF and its homolog D-DT cooperatively suppress p53, providing a mechanistic basis for MIF's oncogenic survival function via ROS/AMPK.

    Evidence Dual siRNA knockdown of MIF and D-DT, p53 phosphorylation Western blots, ROS measurement, AMPK inhibitor experiments, transformation assays

    PMID:24932684

    Open questions at the time
    • Direct biochemical target of MIF/D-DT upstream of ROS not identified
    • Functional redundancy boundaries between MIF and D-DT unresolved
  8. 2015 High

    Identified a C-terminal O-GlcNAcylation that diverts secreted MIF to antagonize EGFR, revealing PTM-gated functional specialization of MIF pools.

    Evidence Mass spectrometry PTM mapping, Ser112/Thr113 mutagenesis, MIF-EGFR binding, invasion/proliferation/tumor assays, MMP13 secretion

    PMID:26280537

    Open questions at the time
    • Enzyme adding the O-GlcNAc and its regulation not defined
    • Balance between EGFR-antagonist and CD74-agonist MIF pools in vivo unknown
  9. 2016 High

    Expanded the receptor repertoire (CD44) and identified the dominant transcriptional driver ICBP90/UHRF1 at the disease-associated −794 CATT microsatellite, plus RORα as a direct regulator, connecting MIF genetics to expression.

    Evidence Co-IP of CD74/CD44, RhoA and invasion assays; affinity chromatography + LC-MS/MS and shRNA for ICBP90; ChIP and ligand assays for RORα; microglial signaling assays

    PMID:26752645 PMID:27157615 PMID:27872288 PMID:27925372

    Open questions at the time
    • Interplay among CD74/CXCR4/CD44 receptor configurations not unified
    • How CATT repeat length mechanistically alters ICBP90 binding not resolved
  10. 2017 Medium

    Identified MIF as the first endogenous HTRA1 inhibitor, adding a protease-regulatory function distinct from cytokine signaling.

    Evidence Co-IP, in vitro protease inhibition assay, astrocyte co-localization by immunohistochemistry

    PMID:28726057

    Open questions at the time
    • Structural basis of MIF–HTRA1 inhibition not determined
    • Physiological consequences of the interaction not established in vivo
  11. 2018 Medium

    Defined cell-type-specific and context-dependent MIF signaling outputs—endothelial MIF relaxing pericytes for neutrophil transit, and soluble CD74 rerouting MIF/CXCR4 survival signaling to necroptosis.

    Evidence EC-specific MIF conditional KO with myosin light chain phosphorylation and BAL counts; sCD74+MIF co-treatment of cardiac fibroblasts with RIP1/RIP3 inhibitors and gene profiling

    PMID:30252532 PMID:30371153

    Open questions at the time
    • Mechanism by which sCD74 switches AKT survival to RIP1/RIP3 death not defined
    • Receptor configuration for endothelial MIF effect on pericytes not mapped
  12. 2021 High

    Revealed an intracellular enzymatic function—MIF is a 3' flap nuclease acting at replication forks—establishing a moonlighting role wholly distinct from cytokine signaling.

    Evidence In vitro nuclease assay, nuclear fractionation, PARP1 co-localization, and nuclease-dead mutant rescue in MIF-knockdown cancer cells

    PMID:34012010

    Open questions at the time
    • Trigger for S-phase nuclear translocation not defined
    • Relationship between nuclease and cytokine functions of the same protein unresolved
  13. 2022 High

    Showed that K78 acetylation status, controlled by HDAC6, gates MIF–AIF binding and nuclear translocation, providing a switch governing MIF's intracellular pro-death function.

    Evidence Mass spectrometry K78 acetylation mapping, MIF-AIF co-IP, K78Q knock-in mice, HDAC6 ablation/inhibition, nuclear fractionation in ischemic neurons

    PMID:35585040

    Open questions at the time
    • Acetyltransferase opposing HDAC6 not identified
    • Link between K78-controlled AIF binding and the flap-nuclease function not integrated
  14. 2024 Medium

    Added a mitochondrial quality-control role: MIF binds PINK1 to block PINK1–Parkin coupling and mitophagy, expanding MIF's intracellular interactome and cell-death control.

    Evidence MIF-PINK1 co-IP, ISO-1 inhibition and overexpression, mitophagy flux and apoptosis assays in renal tubular cells; PLA visualization of CD74/CXCR4 on CD4+ T cells

    PMID:38956064 PMID:38992165

    Open questions at the time
    • Whether PINK1 binding requires specific MIF PTMs or localization not addressed
    • Direct vs indirect mechanism of PINK1–Parkin disruption not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single small protein partitions between secreted cytokine, intracellular flap nuclease, protease inhibitor, and mitophagy regulator—and how PTMs (O-GlcNAc, K78 acetylation) coordinate these fates—remains unresolved.
  • No unified model linking MIF's enzymatic and signaling functions
  • No structural framework integrating receptor binding, nuclease activity, and protein-interaction surfaces
  • Tissue-level balance of pro- vs anti-tumor and pro- vs anti-survival MIF activities undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 2 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005576 extracellular region 4 GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 1
Partners
AIFCD44CD74CXCR4EGFRHTRA1PARP1PINK1
Complex memberships
CD74/CD44 receptor complexCD74/CXCR4 receptor complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 CD74, a Type II transmembrane protein, is a high-affinity receptor for MIF. MIF binds to the extracellular domain of CD74 with a dissociation constant of ~9×10⁻⁹ M (by surface plasmon resonance), and CD74 is required for MIF-induced ERK1/2 MAP kinase activation, cell proliferation, and PGE2 production. Expression cloning, surface plasmon resonance (BIAcore), functional cell-based assays with soluble CD74 as inhibitor The Journal of experimental medicine High 12782713
1994 Recombinant human and mouse MIF are bioactive 12.5 kDa proteins with no significant post-translational modifications; both inhibit monocyte migration, induce TNF-α secretion, and stimulate nitric oxide production by IFN-γ-primed macrophages. Circular dichroism reveals significant β-sheet and α-helix secondary structure. Recombinant protein expression and purification, gel electrophoresis, mass spectrometry, bioactivity assays (Boyden chamber, cytokine ELISA), circular dichroism spectroscopy, guanidine denaturation Biochemistry High 7947826
2009 MIF triggers leukocyte recruitment through CXCR4; CD74 forms functional heteromeric complexes with CXCR4 at the cell surface of monocytes, and MIF-stimulated CD74-dependent AKT activation is blocked by anti-CXCR4 antibody and AMD3100, whereas CXCL12-stimulated AKT activation is not blocked by anti-CD74, indicating MIF-specific signaling through the CD74/CXCR4 complex. Co-immunoprecipitation of endogenous CD74/CXCR4 complexes from monocytes; HEK293 overexpression; receptor-specific antibody and small-molecule inhibitor blockade; AKT phosphorylation assay FEBS letters High 19665027
2009 MIF-induced neutrophil accumulation in the alveolar space is mediated through CD74 expressed on alveolar macrophages, which activates p44/p42 MAPK and chemokine (MIP-2) release; anti-CD74 antibody inhibits MIF-induced MAPK phosphorylation, MIP-2 release, and neutrophil accumulation in vivo. Intratracheal instillation of recombinant MIF in mice ± anti-CD74 antibody or ISO-1; macrophage culture; ELISA; BAL cell counting Respiratory research Medium 19413900
2008 CD74 acts as a functional receptor for MIF in human podocytes; MIF binding to CD74 leads to phosphorylation of ERK1/2 and p38, and MIF induces expression of TRAIL and MCP-1 in podocytes and proximal tubule cells in a p38-dependent manner. High glucose and TNF-α upregulate CD74 surface expression. Cell surface CD74 expression by flow cytometry; MIF stimulation of cultured podocytes; Western blot for ERK1/2 and p38 phosphorylation; cytokine ELISA; pharmacological inhibition of p38 Journal of the American Society of Nephrology Medium 18842989
2016 MIF increases CD44 expression in synovial fibroblasts, promotes CD44 recruitment into a functional CD74/CD44 signal transduction complex, and stimulates alternative exon splicing to produce CD44v3-v6 isoforms associated with invasive phenotypes. CD44 recruitment, downstream MAPK and RhoA signaling, and invasive phenotype all require MIF and CD74. MIF stimulation of synovial fibroblasts; Western blot; co-immunoprecipitation; RT-PCR splicing analysis; RhoA activity assay; invasion assay; MIF pathway antagonist treatment and shRNA knockdown Proceedings of the National Academy of Sciences of the United States of America Medium 27872288
2016 MIF-CD74 signaling inhibits IFN-γ secretion in microglia through phosphorylation of ERK1/2, thereby suppressing microglial M1 polarization; siRNA-mediated knockdown or antibody neutralization of MIF or CD74 promotes IFN-γ release, induces M2→M1 shift, and prolongs survival in glioma-implanted mice. siRNA knockdown; antibody neutralization; Western blot for ERK1/2 phosphorylation; cytokine ELISA; in vivo glioma implantation model; survival analysis Oncogene Medium 27157615
2002 MIF secretion is induced by cell adhesion to fibronectin in quiescent fibroblasts; secreted MIF acts as an autocrine mediator of integrin-dependent MAP kinase activation, cyclin D1 expression, and DNA synthesis. MIF secretion requires protein kinase C activity, and MIF-deficient cells show significantly higher Rb tumor suppressor and lower E2F transcriptional activities. MIF-null mouse fibroblasts; recombinant MIF reconstitution; PKC inhibition; Western blot; cyclin D1 reporter; DNA synthesis assay; Rb/E2F activity assays The Journal of biological chemistry Medium 12297513
2015 MIF is O-GlcNAcylated at Ser112/Thr113 at its C-terminus; the naturally secreted O-GlcNAcylated MIF binds to EGFR and inhibits EGF binding and EGF-induced EGFR activation, ERK and c-Jun phosphorylation, cell invasion, proliferation, and brain tumor formation. EGFR activation enhances secretion of MMP13, which degrades extracellular MIF, creating a feedforward loop. Mass spectrometry identification of O-GlcNAcylation site; binding assays (MIF-EGFR interaction); functional assays (proliferation, invasion, tumor formation); site-directed mutagenesis at Ser112/Thr113; MMP13 secretion assay Nature cell biology High 26280537
2021 MIF is a 3' flap nuclease that translocates to the nucleus during S phase; PARP1 co-localizes with MIF at the DNA replication fork, and MIF nuclease activity is required to resolve replication stress. MIF loss causes increased mutation frequency, cell cycle delays, and inhibition of DNA synthesis that cannot be rescued by nuclease-deficient MIF mutant. In vitro nuclease assay; nuclear fractionation; co-localization by imaging; cell cycle analysis; DNA synthesis assay; mutant MIF rescue experiment; cancer cell MIF knockdown Nature communications High 34012010
2016 The transcription factor ICBP90 (UHRF1) is the major nuclear protein interacting with the MIF -794 CATT5-8 microsatellite promoter region and is essential for MIF transcription in monocytes/macrophages, B and T lymphocytes, and synovial fibroblasts; TLR-induced MIF transcription is regulated in an ICBP90- and CATT repeat length-dependent manner. Oligonucleotide affinity chromatography; LC-MS/MS protein identification; ICBP90 shRNA knockdown; promoter reporter assays; whole-genome transcription analysis The Journal of clinical investigation High 26752645
2006 Hypoxia-induced MIF expression is driven by HIF-1α through a hypoxia response element (HRE) in the 5'UTR of the MIF gene, and this expression is further modulated by CREB; hypoxia-induced degradation of CREB amplifies HIF-1-driven MIF transcription. HIF-1α overexpression; HRE reporter assay; CREB expression modulation; promoter deletion analysis; RT-PCR Biochemical and biophysical research communications Medium 16854377
2018 Soluble CD74 (sCD74) reroutes MIF/CXCR4/AKT-mediated survival of cardiac myofibroblasts to necroptosis via RIP1/RIP3-dependent pathway; sCD74 diminishes MIF-mediated AKT activation and triggers p38 activation, and co-treatment with MIF and sCD74 induces interferon-stimulated gene upregulation. Recombinant MIF + sCD74 co-treatment of primary cardiac fibroblasts; Western blot for AKT and p38; RIP1/RIP3 inhibitor studies; microarray + RT-qPCR gene expression Journal of the American Heart Association Medium 30371153
2017 MIF directly binds to and inhibits the proteolytic activity of the serine protease HTRA1, making MIF the first identified endogenous inhibitor of HTRA1. Both proteins are co-expressed in astrocytes and the interaction modulates availability of growth factors and extracellular matrix molecules affecting cell growth and differentiation. Co-immunoprecipitation; in vitro protease activity assay with MIF as inhibitor; immunohistochemistry co-localization in astrocytes Cellular and molecular life sciences Medium 28726057
2022 HDAC6 deacetylates MIF at K78; HDAC6 inhibition or aspirin treatment promotes MIF acetylation at K78, which suppresses the interaction between MIF and AIF (apoptosis-inducing factor), thereby impairing MIF nuclear translocation in ischemic cortical neurons and reducing neuronal DNA fragmentation and death. Mass spectrometry identification of K78 acetylation; co-immunoprecipitation of MIF-AIF interaction; MIF K78Q acetylation-mimetic knock-in mice; HDAC6 genetic ablation and pharmacological inhibition; fractionation for nuclear localization Cell death & disease High 35585040
2024 MIF directly binds PINK1, disrupting the PINK1-Parkin protein interaction; this blocks Parkin recruitment to mitochondria and inhibits mitophagy initiation in renal tubular epithelial cells, leading to apoptosis that can be reversed by the MIF inhibitor ISO-1. Co-immunoprecipitation of MIF-PINK1 interaction; MIF inhibition (ISO-1) and overexpression; Western blot for PINK1-Parkin interaction; mitophagy flux assays; apoptosis assay Cell death & disease Medium 38956064
2016 RORα (nuclear receptor) directly occupies the MIF promoter region in THP-1 monocytes and HUVEC cells, and RORα ligand treatment modulates MIF expression, identifying MIF as a direct transcriptional target of RORα. Chromatin immunoprecipitation (ChIP) assay; RORα-specific ligand (CPG 52608, SR1001) treatment; RT-PCR gene expression analysis Cell biology international Medium 27925372
2014 MIF and its homolog D-DT synergistically inhibit steady-state p53 phosphorylation, stabilization, and transcriptional activity; combined siRNA loss of MIF and D-DT leads to dramatically reduced cell cycle progression, anchorage independence, focus formation, and increased apoptosis compared to individual loss. The p53 activation is dependent on reactive oxygen species (ROS) that mediate aberrant AMPK activation in MIF/D-DT-deficient cells. siRNA dual knockdown of MIF and D-DT; Western blot for p53 phosphorylation; cell cycle analysis; focus formation and soft-agar assays; ROS measurement; AMPK inhibitor experiments PloS one Medium 24932684
2005 MIF loss delays Myc-induced B-cell lymphoma development in vivo by perturbing E2F DNA-binding activity and enhancing p53 pathway tumor suppressor activity; MIF-deficient premalignant B-cells show delayed S-phase progression and increased apoptosis, and MIF-deficient lymphomas that do arise carry ARF deletions and p53 inactivating mutations. Eμ-Myc lymphoma mouse model with MIF-null background; E2F DNA-binding activity assay; p53 pathway activity; cell cycle analysis; tumor onset kinetics Cell death and differentiation Medium 15947793
2009 MIF acts as an autocrine growth factor in pancreatic cancer cells; siRNA-mediated MIF silencing reduces MIF protein >85%, inhibits cellular proliferation, induces apoptosis, and is accompanied by increased AKT phosphorylation at Thr308. siRNA knockdown; qRT-PCR; Western blot; FACS apoptosis assay; AKT phosphorylation Western blot The Journal of surgical research Low 19726058
2024 CD74 is upregulated on activated CD4+ T cells by post-translational modification (chondroitin sulfate addition) and can be detected on the cell surface; CD74/CXCR4 heterocomplexes on activated CD4+ T cells are visualized by proximity ligation assay, and both CD74 and CXCR4 are causally involved in MIF-induced CD4+ T-cell migration as shown by receptor-specific inhibitors in 3D live cell imaging. Flow cytometry; Western blot; proximity ligation assay; 3D-matrix live cell imaging; receptor-specific pathway inhibitors; reanalysis of RNA-seq and proteomics datasets Cellular and molecular life sciences Medium 38992165
2013 CD74 is required for MIF's inhibitory effect on osteoclastogenesis; MIF inhibits osteoclast formation from wild-type but not CD74-knockout bone marrow cultures, and CD74-deficient mice show decreased bone mass, increased osteoclast number and area, and reduced NFATc1 and c-Fos expression upon MIF treatment. CD74 knockout mice; in vitro osteoclast differentiation assay; micro-CT; histomorphometry; Western blot for NFATc1 and c-Fos Journal of bone and mineral research Medium 23044992
2018 Endothelial cell-derived MIF decreases pericyte contractility by reducing myosin light chain phosphorylation and increases intercellular pericyte gap formation, thereby enhancing neutrophil transmigration; EC-specific MIF knockout mice show decreased neutrophil infiltration to BAL and lung tissue and increased myosin light chain phosphorylation in pericytes in acute lung injury. EC-specific MIF conditional knockout mice; in vitro microvascular model; myosin light chain phosphorylation Western blot; silicone substrate contractility assay; bronchoalveolar lavage cell counting FASEB journal Medium 30252532
2009 MIF induces MIP-2 accumulation in alveolar macrophages through p44/p42 MAPK activation downstream of CD74; MIF-induced MAPK phosphorylation and MIP-2 release by macrophages are blocked by anti-CD74 antibody. Macrophage culture; MIF stimulation; anti-CD74 antibody blockade; Western blot for p44/p42 MAPK phosphorylation; ELISA for MIP-2 Respiratory research Medium 19413900
2016 4-IPP (MIF inhibitor) blocks MIF/CD74 internalization, activates JNK, dose-dependently inhibits proliferation, and induces apoptosis and mitotic cell death in thyroid carcinoma cells co-expressing MIF and CD74; effects are partially reduced in CD74-negative cells. 4-IPP pharmacological inhibition; cell viability assay; Western blot for JNK activation; flow cytometry for apoptosis; immunohistochemistry of patient samples Endocrine-related cancer Low 26206776

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 MIF signal transduction initiated by binding to CD74. The Journal of experimental medicine 941 12782713
1994 Purification, bioactivity, and secondary structure analysis of mouse and human macrophage migration inhibitory factor (MIF). Biochemistry 378 7947826
2021 Macrophage migration inhibitory factor (MIF): A multifaceted cytokine regulated by genetic and physiological strategies. Pharmacology & therapeutics 240 34673115
2019 The immunobiology of MIF: function, genetics and prospects for precision medicine. Nature reviews. Rheumatology 217 31197253
2019 Evolving complexity of MIF signaling. Cellular signalling 204 30682543
2009 A functional heteromeric MIF receptor formed by CD74 and CXCR4. FEBS letters 202 19665027
2010 Macrophage migration inhibitory factor (MIF): a promising biomarker. Drug news & perspectives 199 20520854
2000 Macrophage migration inhibitory factor (MIF): its essential role in the immune system and cell growth. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 176 11032394
2012 D-dopachrome tautomerase (D-DT or MIF-2): doubling the MIF cytokine family. Cytokine 150 22507380
1997 Macrophage migration inhibitory factor (MIF): a glucocorticoid counter-regulator within the immune system. Critical reviews in immunology 143 9034724
2020 MIF-Dependent Control of Tumor Immunity. Frontiers in immunology 142 33324425
2016 Targeting MIF in Cancer: Therapeutic Strategies, Current Developments, and Future Opportunities. Medicinal research reviews 139 26777977
2019 Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus. Expert opinion on therapeutic targets 130 31414920
1998 MIF expression in the rat brain: implications for neuronal function. Molecular medicine (Cambridge, Mass.) 128 9606175
2016 MIF-CD74 signaling impedes microglial M1 polarization and facilitates brain tumorigenesis. Oncogene 117 27157615
2004 Mechanisms and effectors of MIF-dependent promotion of tumourigenesis. Cellular signalling 113 14607271
2006 Dual regulation of macrophage migration inhibitory factor (MIF) expression in hypoxia by CREB and HIF-1. Biochemical and biophysical research communications 110 16854377
2020 Exosomes from mesenchymal stem cells overexpressing MIF enhance myocardial repair. Journal of cellular physiology 109 31960418
2008 Role of MIF in inflammation and tumorigenesis. Oncology 109 18791328
2015 A Secreted MIF Cytokine Enables Aphid Feeding and Represses Plant Immune Responses. Current biology : CB 105 26119751
2009 Macrophage CD74 contributes to MIF-induced pulmonary inflammation. Respiratory research 104 19413900
2008 The MIF receptor CD74 in diabetic podocyte injury. Journal of the American Society of Nephrology : JASN 101 18842989
2019 MIF family proteins in genitourinary cancer: tumorigenic roles and therapeutic potential. Nature reviews. Urology 95 30914802
2000 Enhancement of macrophage migration inhibitory factor (MIF) expression in injured epidermis and cultured fibroblasts. Biochimica et biophysica acta 95 10564712
2012 Macrophage migration inhibitory factor (MIF) promotes cell survival and proliferation of neural stem/progenitor cells. Journal of cell science 92 22454509
1995 Cloning and characterization of the gene for mouse macrophage migration inhibitory factor (MIF). Journal of immunology (Baltimore, Md. : 1950) 92 7706726
2013 The vascular biology of macrophage migration inhibitory factor (MIF). Expression and effects in inflammation, atherogenesis and angiogenesis. Thrombosis and haemostasis 84 23329140
2016 MIF-Induced Stromal PKCβ/IL8 Is Essential in Human Acute Myeloid Leukemia. Cancer research 79 27872094
2016 MIF allele-dependent regulation of the MIF coreceptor CD44 and role in rheumatoid arthritis. Proceedings of the National Academy of Sciences of the United States of America 75 27872288
2019 Rediscovering MIF: New Tricks for an Old Cytokine. Trends in immunology 74 30962001
2011 Macrophage migration inhibitory factor (MIF): a key player in protozoan infections. International journal of biological sciences 74 22110378
2005 Role of macrophage migration inhibitory factor (MIF) in the skin. Journal of dermatological science 68 15659324
2011 MIF: a key player in cutaneous biology and wound healing. Experimental dermatology 65 21158933
2012 MIF, CD74 and other partners in kidney disease: tales of a promiscuous couple. Cytokine & growth factor reviews 64 22959722
2012 MIF, MIF alleles, and prospects for therapeutic intervention in autoimmunity. Journal of clinical immunology 64 22968741
2008 Chemokine-like functions of MIF in atherosclerosis. Journal of molecular medicine (Berlin, Germany) 62 18385967
2006 Insight into the biology of macrophage migration inhibitory factor (MIF) revealed by the cloning of its cell surface receptor. Cell research 62 16474429
2015 MIF: Implications in the Pathoetiology of Systemic Lupus Erythematosus. Frontiers in immunology 61 26617609
2019 Role of Macrophage Migration Inhibitory Factor (MIF) in Melanoma. Cancers 56 31013837
2017 Macrophage Migration Inhibitory Factor (MIF): A Glucocorticoid Counter-Regulator within the Immune System. Critical reviews in immunology 56 29773026
2015 Secreted and O-GlcNAcylated MIF binds to the human EGF receptor and inhibits its activation. Nature cell biology 56 26280537
2018 Soluble CD74 Reroutes MIF/CXCR4/AKT-Mediated Survival of Cardiac Myofibroblasts to Necroptosis. Journal of the American Heart Association 54 30371153
2016 Transcription factor ICBP90 regulates the MIF promoter and immune susceptibility locus. The Journal of clinical investigation 54 26752645
2001 Neuroendocrine properties of macrophage migration inhibitory factor (MIF). Immunology and cell biology 52 11488984
2015 MIF and CXCL12 in Cardiovascular Diseases: Functional Differences and Similarities. Frontiers in immunology 50 26257740
2017 MIF/CD74 axis is a target for novel therapies in colon carcinomatosis. Journal of experimental & clinical cancer research : CR 49 28114961
2001 Macrophage migration inhibitory factor (MIF) modulates innate immune responses induced by endotoxin and Gram-negative bacteria. Journal of endotoxin research 49 11753217
2006 Tumor-derived macrophage migration inhibitory factor (MIF) inhibits T lymphocyte activation. Cytokine 48 16522371
2002 Adhesion-dependent signaling by macrophage migration inhibitory factor (MIF). The Journal of biological chemistry 47 12297513
2024 CD74 is a functional MIF receptor on activated CD4+ T cells. Cellular and molecular life sciences : CMLS 46 38992165
2016 The non-mammalian MIF superfamily. Immunobiology 46 27780588
2009 Inhibition of MIF leads to cell cycle arrest and apoptosis in pancreatic cancer cells. The Journal of surgical research 46 19726058
2020 The Role of MIF on Eosinophil Biology and Eosinophilic Inflammation. Clinical reviews in allergy & immunology 45 30680604
2014 HLA-DRα1 constructs block CD74 expression and MIF effects in experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md. : 1950) 44 24683185
2013 Deletion of CD74, a putative MIF receptor, in mice enhances osteoclastogenesis and decreases bone mass. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 41 23044992
2014 MIF contributes to Trypanosoma brucei associated immunopathogenicity development. PLoS pathogens 40 25255103
2014 MIF family members cooperatively inhibit p53 expression and activity. PloS one 39 24932684
2016 Predicted structure of MIF/CD74 and RTL1000/CD74 complexes. Metabolic brain disease 37 26851955
2021 MIF is a 3' flap nuclease that facilitates DNA replication and promotes tumor growth. Nature communications 35 34012010
2011 MIF participates in Toxoplasma gondii-induced pathology following oral infection. PloS one 35 21977228
2020 The role of MIF in chronic lung diseases: looking beyond inflammation. American journal of physiology. Lung cellular and molecular physiology 34 32208924
2016 CHD7 promotes proliferation of neural stem cells mediated by MIF. Molecular brain 34 27955690
2014 MIF and CD74 - suitability as clinical biomarkers. Mini reviews in medicinal chemistry 34 25643609
2001 Sharable representation of clinical guidelines in GLIF: relationship to the Arden Syntax. Journal of biomedical informatics 34 11723699
2023 Obacunone targets macrophage migration inhibitory factor (MIF) to impede osteoclastogenesis and alleviate ovariectomy-induced bone loss. Journal of advanced research 33 36657717
2018 Endothelial cell-secreted MIF reduces pericyte contractility and enhances neutrophil extravasation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 30252532
2005 MIF loss impairs Myc-induced lymphomagenesis. Cell death and differentiation 32 15947793
2009 Glucocorticoid-induced MIF expression by human CEM T cells. Cytokine 31 19646897
2018 Macrophage Migration Inhibitory Factor (MIF) Drives Murine Psoriasiform Dermatitis. Frontiers in immunology 29 30333830
2015 4-IPP, a selective MIF inhibitor, causes mitotic catastrophe in thyroid carcinomas. Endocrine-related cancer 29 26206776
2007 From MIF-1 to endomorphin: the Tyr-MIF-1 family of peptides. Peptides 29 17988762
2021 Isopsoralen ameliorates rheumatoid arthritis by targeting MIF. Arthritis research & therapy 28 34535196
2020 Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF-2 in adipose tissue during endotoxemia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 31961019
2019 Macrophage Migration Inhibitory Factor (MIF) Expression Increases during Myocardial Infarction and Supports Pro-Inflammatory Signaling in Cardiac Fibroblasts. Biomolecules 28 30678084
2023 MIF is a critical regulator of mononuclear phagocytic infiltration in hepatocellular carcinoma. iScience 27 37520719
2022 The IL-25-dependent tuft cell circuit driven by intestinal helminths requires macrophage migration inhibitory factor (MIF). Mucosal immunology 27 35288645
2007 MIF coordinates the cell cycle with DNA damage checkpoints. Lessons from knockout mouse models. Cell division 26 17640378
2022 Macrophage migration inhibitory factor (MIF) acetylation protects neurons from ischemic injury. Cell death & disease 25 35585040
2019 MIF promotes perineural invasion through EMT in salivary adenoid cystic carcinoma. Molecular carcinogenesis 25 30667094
2024 Macrophage migration inhibitory factor (MIF) suppresses mitophagy through disturbing the protein interaction of PINK1-Parkin in sepsis-associated acute kidney injury. Cell death & disease 24 38956064
2021 Recombinant Mycobacterium smegmatis delivering a fusion protein of human macrophage migration inhibitory factor (MIF) and IL-7 exerts an anticancer effect by inducing an immune response against MIF in a tumor-bearing mouse model. Journal for immunotherapy of cancer 24 34389619
2018 Circulating macrophage migration inhibitory factor (MIF) in patients with heart failure. Cytokine 23 29723777
2017 Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1. Cellular and molecular life sciences : CMLS 23 28726057
2020 Immune modulation by the macrophage migration inhibitory factor (MIF) family: D-dopachrome tautomerase (DDT) is not (always) a backup system. Cytokine 22 32417648
2018 Mif-deficiency favors an atheroprotective autoantibody phenotype in atherosclerosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22 29543531
2017 Invariant Chain Complexes and Clusters as Platforms for MIF Signaling. Cells 22 28208600
2000 Macrophage migration inhibitory factor (MIF) as a paracrine mediator in the interaction of testicular somatic cells. Andrologia 22 10702866
2021 Macrophage migration inhibitory factor (MIF) enhances hypochlorous acid production in phagocytic neutrophils. Redox biology 21 33823474
2017 Associations between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis, and between MIF gene polymorphisms and disease susceptibility: a meta-analysis. Postgraduate medical journal 21 28912189
2011 MIF from mussel: coding sequence, phylogeny, polymorphism, 3D model and regulation of expression. Developmental and comparative immunology 20 22085783
1998 Neuroimmunomodulation by macrophage migration inhibitory factor (MIF). Annals of the New York Academy of Sciences 19 9629239
1994 Differential metabolism of Tyr-MIF-1 and MIF-1 in rat and human plasma. Biochemical pharmacology 19 7907473
1987 MIF-1 and Tyr-MIF-1 augment GABA-stimulated benzodiazepine receptor binding. Peptides 19 2893356
2024 Macrophage migration inhibitor factor (MIF): Potential role in cognitive impairment disorders. Cytokine & growth factor reviews 18 38548489
2020 Macrophage inhibitory factor (MIF) gene polymorphisms are associated with disease susceptibility and with circulating MIF levels in active non-segmental vitiligo in patients from western Mexico. Molecular genetics & genomic medicine 17 32705792
2017 CYP19A1, MIF and ABCA1 genes are targets of the RORα in monocyte and endothelial cells. Cell biology international 17 27925372
2014 Stromal-dependent tumor promotion by MIF family members. Cellular signalling 17 25277536
2009 Structural and functional comparison of MIF ortholog from Plasmodium yoelii with MIF from its rodent host. Molecular immunology 17 20004020
2006 Increasing expression of GST-pi MIF, and ID1 genes in chemoresistant prostate cancer cells. Archives of andrology 17 16728343
2013 Association between MIF gene polymorphisms and carotid artery atherosclerosis. Biochemical and biophysical research communications 16 23537651

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