Affinage

TFRC

Transferrin receptor protein 1 · UniProt P02786

Length
760 aa
Mass
84.9 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TFRC (TfR1/CD71) is the principal cell-surface receptor for transferrin-bound iron uptake, and the depth of its post-translational, transcriptional, and trafficking regulation positions it as a central control node for cellular labile iron and, consequently, for ferroptosis (PMID:26642240, PMID:37683766). Receptor internalization depends on an intact tyrosine-based motif: a homozygous p.Tyr20His substitution disrupts endocytosis, raises surface TfR1, impairs transferrin uptake, and causes a combined immunodeficiency that is rescued by iron citrate and by wild-type but not mutant TfR1, establishing iron-dependent lymphocyte activation as a nonredundant TfR1 function (PMID:26642240). Beyond constitutive iron import, TfR1 abundance and activity are tuned by multiple modifications—stearoylation that restrains JNK signaling and promotes mitochondrial fusion via HUWE1/mitofusin (PMID:26214738), O-GlcNAcylation at Ser687 that licenses MARCH8 binding and Lys665 polyubiquitination (PMID:38744192), and DHHC5-mediated palmitoylation at Cys98 that sets endocytosis rate in oligodendrocytes (PMID:39929269). Protein levels are further set by ubiquitin-dependent degradation through NEDD4L and βTrCP and by autophagic turnover, with multiple E3 ligases and adaptors converging on TfR1 to lower the labile iron pool and suppress ferroptosis (PMID:34315867, PMID:38302612, PMID:35613689, PMID:38744192). TFRC mRNA is regulated by m6A methylation (METTL3 writing, IGF2BP2 stabilizing, YTHDF1 enhancing translation, FTO demethylating) and by NAT10-dependent ac4C acetylation, while its transcription is driven by HIF-1/HIF-2α, Sp1, ATF3, and Ahr and is restrained by repressive H3K9me3 chromatin (PMID:38631119, PMID:38834654, PMID:33204330, PMID:39251905, PMID:37324938, PMID:38808263, PMID:35821227, PMID:37709985, PMID:36960698). Through these inputs, excess TfR1-mediated iron import drives ferroptosis across diverse tissues, whereas physiological TfR1 also supports systemic iron homeostasis via an HFE-dependent hepatocyte function controlling hepcidin, contributes to ineffective erythropoiesis in β-thalassemia, and supports regulatory T cell and ILC3 expansion and metabolic programming (PMID:36322932, PMID:28151426, PMID:38954474, PMID:37709985). TfR1 additionally engages non-canonical partners—the IKK complex to sustain NF-κB signaling and the myokine Musclin to gate cAMP/PKA-dependent adipocyte thermogenesis (PMID:23016877, PMID:37468484).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2009 Low

    Early work placed TFRC expression downstream of growth and developmental signaling, framing it as an inducible rather than purely housekeeping gene.

    Evidence Wnt-3a stimulation time-course in C57MG cells; miR-320 enforced expression in HL-60 cells

    PMID:19135902 PMID:19353769

    Open questions at the time
    • Wnt linkage is correlative time-course with no direct promoter mechanism
    • miR-320 target validation lacks a direct 3'UTR reporter
  2. 2013 Medium

    Established that TfR1 has a signaling role beyond iron import by physically scaffolding the IKK complex to sustain NF-κB-dependent transcription and protect against TNFα-induced apoptosis.

    Evidence Unbiased proteomics, reciprocal Co-IP, siRNA knockdown, NF-κB reporter and chromatin binding assays

    PMID:23016877

    Open questions at the time
    • Structural basis of TfR1-IKK contact unresolved
    • Whether iron import is required for the NF-κB effect not separated
  3. 2015 High

    Defined the genetic and structural requirement for TfR1 endocytosis in human disease, showing that a Tyr20 motif mutation causes combined immunodeficiency through defective receptor internalization rescuable by iron.

    Evidence Patient fibroblast rescue, Tfrc(Y20H/Y20H) knock-in mice, endocytosis assays, STEAP3 Co-IP

    PMID:26642240

    Open questions at the time
    • STEAP3 accessory endocytosis signal only partially defined
    • Tissue specificity of the immune phenotype not fully explained
  4. 2015 High

    Revealed a lipid-modification arm of TfR1 regulation in which stearoylation suppresses TfR1-driven JNK signaling and promotes mitochondrial fusion, linking dietary fatty acids to mitochondrial dynamics.

    Evidence In vivo dietary C18:0 manipulation, Drosophila genetics, stearoylation biochemistry, mitofusin ubiquitination assay

    PMID:26214738

    Open questions at the time
    • Stearoylation site on TfR1 not mapped here
    • Connection between stearoylation and canonical iron uptake unaddressed
  5. 2017 High

    Demonstrated that TfR1 dosage in erythroid precursors drives ineffective erythropoiesis, with haploinsufficiency correcting iron overload in β-thalassemia.

    Evidence TfR1+/- × β-thalassemia mouse crosses, erythroid culture with apotransferrin, flow cytometry, in vivo iron measures

    PMID:28151426

    Open questions at the time
    • Mechanism of apotransferrin suppression of TfR1 not molecularly defined
    • Human translatability not tested
  6. 2023 High

    Showed that hepatocyte TfR1's role in systemic iron homeostasis and hepcidin regulation is strictly HFE-dependent, resolving the in vivo partnership controlling iron sensing.

    Evidence Hepatocyte-specific Tfrc knockout, Tfrc/Hfe double knockout epistasis, β-thalassemia model, iron and hepcidin quantification

    PMID:36322932

    Open questions at the time
    • Molecular details of TfR1-HFE-mediated hepcidin signaling not dissected here
    • Other hepatic iron sensors not excluded
  7. 2023 High

    Extended TfR1 function into immune and metabolic programming, establishing transcriptional repression by Ahr controls ILC3 iron metabolism and a Musclin-TfR1 axis that gates adipocyte thermogenesis.

    Evidence Tfrc conditional ablation in ILC3, Ahr ChIP and genetic ablation, metabolic assays; Musclin binding and muscle-specific KO mice with cAMP/PKA readouts

    PMID:37468484 PMID:37709985

    Open questions at the time
    • Whether Musclin and transferrin compete for TfR1 not defined
    • How iron flux couples to OXPHOS-glycolysis switch mechanistically open
  8. 2024 High

    Defined a Treg-intrinsic requirement for TfR1, showing iron uptake supports perinatal Treg expansion and prevents scurfy-like autoimmunity.

    Evidence Treg-specific conditional CD71 knockout, proliferation and tissue-Treg signature analysis, iron and hepcidin measurements

    PMID:38954474

    Open questions at the time
    • Iron-dependent metabolic targets in Tregs not identified
    • Link between Treg iron and systemic hepcidin not fully mechanistic
  9. 2024 High

    Mapped a multilayered code controlling TfR1 protein stability through site-specific O-GlcNAcylation and competing E3 ligase pathways that set the labile iron pool and ferroptosis sensitivity.

    Evidence Ser687/Lys665 mutagenesis, MARCH8 Co-IP and ubiquitination assays; NEDD4L, βTrCP, ESR1, TIMP1, RAB17 ubiquitination/stability studies across cancer and injury models

    PMID:34315867 PMID:35613689 PMID:38302612 PMID:38744192 PMID:39242574 PMID:39578773

    Open questions at the time
    • Hierarchy among competing E3 ligases in a single cell type unresolved
    • Crosstalk between O-GlcNAc, palmitoylation, and ubiquitination not integrated
  10. 2024 High

    Established RNA-level control of TFRC by m6A and ac4C, identifying writers, readers, and erasers that tune TFRC stability and translation to drive or restrain ferroptosis in vivo.

    Evidence METTL3 conditional KO, IGF2BP2/YTHDF1 RIP, FTO target identification, NAT10 ac4C assays across cardiac, hepatic, and pulmonary injury models

    PMID:33204330 PMID:38631119 PMID:38834654 PMID:38996995 PMID:39251905

    Open questions at the time
    • Relative contribution of stabilization versus translational control unclear
    • Whether multiple RNA modifications act on the same transcripts simultaneously untested
  11. 2024 Medium

    Detailed transcriptional and chromatin control converging on the Tfrc promoter, with HIF-1/HIF-2α, Sp1, ATF3, and Kat2a-driven acetylation activating, and Suv39h1/H3K9me3 repressing, transcription to set ferroptosis thresholds.

    Evidence ChIP for transcription factors and histone marks, HDAC9/HIF/Sp1 dissection, Kat2a and Suv39h1 manipulation in ischemia and cardiomyopathy models

    PMID:35821227 PMID:36960698 PMID:37324938 PMID:38764128 PMID:38808263 PMID:38858351

    Open questions at the time
    • Combinatorial logic of these factors at the promoter not resolved
    • Cell-type specificity of repressive versus activating control unclear
  12. 2024 Medium

    Uncovered trafficking and non-iron interactions of TfR1, including palmitoylation-controlled endocytosis, CCT3/ACTN4-dependent recycling, autophagic and EV-mediated turnover, and partnerships with GSK3B and complement C4.

    Evidence DHHC5 palmitoylation site mapping in oligodendrocytes, CCT3-ACTN4-TFRC Co-IP, LDELS/ESCRT/RAB27A EV secretion dissection, GSK3B and C4 Co-IP

    PMID:36286616 PMID:38169212 PMID:38321571 PMID:39210442 PMID:39929269

    Open questions at the time
    • Functional significance of TfR1 EV secretion unknown
    • TfR1-GSK3B and TfR1-C4 interactions rest on single-lab Co-IP

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the numerous parallel regulatory layers — PTMs, competing E3 ligases, RNA modifications, transcription factors, and trafficking machinery — are integrated within a single cell to set TfR1 surface density and iron flux remains unresolved.
  • No unified model reconciling competing degradation and stabilization pathways
  • Quantitative contribution of each layer to net iron uptake unmeasured
  • Structural basis for most non-transferrin partner interactions undetermined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 2 GO:0060089 molecular transducer activity 2 GO:0140104 molecular carrier activity 2
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 2 GO:0005634 nucleus 1 GO:0005764 lysosome 1
Pathway
R-HSA-5357801 Programmed Cell Death 4 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3 R-HSA-382551 Transport of small molecules 3
Partners
C4GSK3BHFEIKKMARCH8MUSCLINNEDD4LSTEAP3

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 A homozygous p.Tyr20His substitution in TfR1 disrupts the TfR1 internalization motif, resulting in defective receptor endocytosis and markedly increased TfR1 surface expression; iron citrate rescued lymphocyte defects, and wild-type but not mutant TfR1 rescued impaired transferrin uptake in patient-derived fibroblasts. STEAP3, a metalloreductase expressed in erythroblasts, was shown to associate with TfR1 and partially rescue transferrin uptake, suggesting an accessory endocytosis signal. Patient-derived fibroblast rescue assay, Co-IP, Tfrc(Y20H/Y20H) knock-in mouse model, endocytosis assays Nature genetics High 26642240
2015 Stearic acid (C18:0) stearoylates TfR1 (TFRC), thereby inhibiting TfR1-mediated activation of JNK signaling. This reduces ubiquitination of mitofusin via HUWE1, promoting mitochondrial fusion and function. Dietary C18:0 intake modulates this pathway in vivo. In vivo dietary manipulation, Drosophila genetic model, biochemical stearoylation assay, JNK signaling readouts, mitofusin ubiquitination assay Nature High 26214738
2013 TfR1 physically interacts with the IKK complex. TfR1 depletion reduces IKK complex formation and inhibits TNFα-induced NF-κB-dependent transcription; NF-κB fails to translocate to the nucleus efficiently, reducing target gene promoter binding and increasing apoptosis in response to TNFα. Unbiased proteomics screen, Co-IP, siRNA knockdown, NF-κB reporter assay, chromatin binding assay, apoptosis assay The Biochemical journal Medium 23016877
2017 Overexpression of TfR1 in β-thalassemic erythroid precursors contributes to ineffective erythropoiesis and iron overload. Apotransferrin inhibits TfR1 expression independently of erythropoietin and iron-related signaling, decreases TfR1 partitioning to reticulocytes during enucleation, and enhances enucleation. Haploinsufficiency of TfR1 (TfR1+/-) crossed into β-thalassemic mice reverses iron overload and improves hepcidin derepression. Mouse genetic crosses (TfR1+/- × β-thalassemia), in vitro erythroid culture with apotransferrin, flow cytometry, in vivo iron measurements Blood High 28151426
2023 Hepatocyte TfR1 interacts with HFE to regulate hepcidin production. Hepatocyte-specific Tfrc knockout in mice leads to reduced serum/liver iron and inappropriately elevated hepcidin relative to iron status, but ablation of hepatocyte Tfrc has no impact on iron phenotype in Hfe knockout mice, demonstrating that TfR1's nonredundant function in systemic iron homeostasis depends on HFE. Ablation of hepatocyte Tfrc in β-thalassemia mice ameliorates hepcidin deficiency and liver iron loading. Hepatocyte-specific conditional Tfrc knockout mice (Tfrcfl/fl;Alb-Cre+), double knockout with Hfe, β-thalassemia mouse model, serum/liver iron measurements, hepcidin quantification Blood High 36322932
2021 TRIB2 desensitizes cells to ferroptosis via the E3 ubiquitin ligase βTrCP, which ubiquitinates TFRC; TRIB2 promotes βTrCP-mediated TFRC ubiquitination and degradation, thereby reducing the labile iron pool. TFRC is required for TRIB2's iron-lowering and anti-ferroptotic effects. TRIB2 and βTrCP knockout/overexpression in liver cancer cells, ubiquitination assay, labile iron pool measurement, ferroptosis induction assays (RSL3, erastin) Cell death discovery Medium 34315867
2022 CVB3 infection induces nuclear translocation of TFRC (normally a cell membrane protein); transcription factor Sp1 binds the TFRC promoter and upregulates TFRC transcription during CVB3 infection, driving ferroptosis via the Sp1/TFRC/Fe axis. HeLa cell time-course CVB3 infection model, immunofluorescence for TFRC localization, ChIP for Sp1 binding to TFRC promoter, siRNA knockdown, iron/lipid peroxidation assays Cell death & disease Medium 35821227
2020 YTHDF1 directly interacts with the 3'UTR and 5'UTR of TFRC mRNA via its methyltransferase domain and positively regulates translation of m6A-modified TFRC mRNA, enhancing iron metabolism in hypopharyngeal squamous cell carcinoma. m6A-seq, RIP-seq, gain- and loss-of-function analyses, iron metabolic assays, transcriptome sequencing Theranostics Medium 33204330
2024 METTL3 promotes m6A modification of TFRC mRNA; the m6A reader IGF2BP2 recognizes this modification and increases TFRC mRNA stability, enhancing iron uptake and ferroptosis in cardiomyocytes during doxorubicin cardiotoxicity. Cardiomyocyte-specific METTL3 knockout reduces TFRC expression and prevents ferroptosis. Conditional METTL3 knockout mice, m6A modification assays, RIP for IGF2BP2-TFRC mRNA interaction, ferroptosis markers, in vivo cardiac function assessment Redox biology High 38631119
2024 FTO demethylase targets ACSL4 and TFRC mRNA; FTO inhibits Acsl4 and Tfrc mRNA stability in an m6A-dependent manner, thereby suppressing ferroptosis during ischemia/reperfusion injury in older livers. Mass spectrometry identification of FTO targets, FTO overexpression in mouse model, m6A mRNA stability assays, ferroptosis markers Nature communications Medium 38834654
2024 METTL3 stabilizes NEDD4L mRNA via m6A methylation, enhancing NEDD4L expression. NEDD4L (E3 ubiquitin ligase) ubiquitinates and degrades TFRC, reducing iron accumulation and neuronal ferroptosis after ischemic stroke. MCAO mouse model, NEDD4L knockout and METTL3 overexpression constructs, co-immunoprecipitation, TFRC half-life/ubiquitination assays, qRT-PCR/western blot Cell biology and toxicology Medium 38302612
2022 ESR1 enhances binding of the E3 ubiquitin ligase NEDD4L to CD71 (TfR1), promoting ubiquitination and degradation of CD71. ESR1 knockdown increases CD71 protein levels and enhances ionizing radiation-induced ferroptosis in breast cancer cells. Immunoprecipitation, ubiquitination assay, ESR1 knockdown, ferroptosis/lipid peroxidation assays, flow cytometry Archives of biochemistry and biophysics Medium 35613689
2024 O-GlcNAcylation of TFRC at serine 687 promotes binding of the ubiquitin E3 ligase MARCH8, leading to polyubiquitination at lysine 665 and TFRC degradation. Erastin-induced de-O-GlcNAcylation of TFRC at Ser687 diminishes MARCH8 binding and decreases TFRC polyubiquitination, thereby stabilizing TFRC and enhancing ferroptosis in HCC cells. Site-directed mutagenesis (Ser687, Lys665), co-immunoprecipitation, ubiquitination assay, O-GlcNAcylation detection, erastin ferroptosis assays Redox biology High 38744192
2022 LC3-dependent EV loading and secretion (LDELS) promotes TFRC secretion via extracellular vesicles. TFRC EV secretion requires MAP1LC3/LC3-conjugation machinery components, multiple ESCRT pathway components, and the small GTPase RAB27A, but is independent of other ATGs involved in classical autophagosome formation. Genetic knockdown of LC3-conjugation machinery, ESCRT components and RAB27A; EV isolation and proteomic analysis (TMT); functional secretion assays Autophagy Medium 36286616
2023 TFEB overexpression upregulates TfR1 synthesis and increases TfR1 localization to lysosomes, facilitating lysosomal iron import and transient iron storage, maintaining low cellular labile iron. TfR1 knockdown reverses the lower labile iron and upregulation of ferritin chains caused by TFEB overexpression, demonstrating TFEB regulates cellular labile iron in a TfR1-dependent manner. TFEB overexpression/knockdown, TfR1 knockdown, lysosomal fractionation, labile iron pool measurement, ferritin western blot Free radical biology & medicine Medium 37683766
2023 HDAC9 binds HIF-1 and deacetylates it, leading to HIF-1 stabilization (via reduced ubiquitination) and increased TfR1 transcription; simultaneously, HDAC9 binds and deacetylates Sp1, leading to Sp1 ubiquitination and reduced GPX4 expression. Both pathways promote neuronal ferroptosis after ischemia. ChIP, co-immunoprecipitation, siRNA knockdown of HDAC9/HIF-1/Sp1, OGD/Rx in vitro model, MCAO in vivo model, western blot, ferroptosis marker quantification International journal of biological sciences Medium 37324938
2023 Musclin (a myokine) binds to Tfr1 on beige adipocytes and antagonizes Tfr1-mediated cAMP/PKA-dependent thermogenic induction, thereby attenuating beige fat thermogenesis. Binding assays, muscle-transgenic and AAV-overexpression mouse models, muscle-specific Musclin knockout mice, cAMP/PKA signaling readouts, thermogenesis measurements Nature communications High 37468484
2023 Aryl hydrocarbon receptor (Ahr) directly binds to the Tfrc promoter to inhibit transcription, establishing a Ahr-CD71-iron axis that controls ILC3 proliferation. CD71-mediated iron metabolism controls ILC3 mitochondrial respiration by switching oxidative phosphorylation toward glycolysis. Tfrc conditional ablation in ILC3s, Ahr genetic ablation/activation, ChIP for Ahr binding to Tfrc promoter, metabolic assays (OXPHOS vs glycolysis), infection model (C. rodentium) Nature immunology High 37709985
2024 CCT3 interacts with ACTN4, hindering recycling of TFRC to the cell membrane and obstructing iron endocytosis. CCT3 inhibition of ferroptosis depends on deubiquitination of non-degradative K6-linked ubiquitination at CCT3-K21 upon sorafenib treatment. CRISPR/Cas9 KO library screen, PTM proteomics, Co-IP of CCT3-ACTN4-TFRC, ubiquitination assays, iron endocytosis assays, in vivo xenograft Journal of experimental & clinical cancer research Medium 39210442
2025 DHHC5 palmitoylates TfR1 at the C98 cysteine site in oligodendrocytes. Neonatal sevoflurane exposure inhibits DHHC5 expression, reducing TfR1 palmitoylation, which enhances TfR1 endocytosis (rather than altering expression level), increases iron uptake and ferroptosis in oligodendrocytes, leading to hypomyelination and cognitive impairment. Specific overexpression of DHHC5 in oligodendrocytes restored TfR1 endocytosis and mitigated these effects. Acyl-resin assisted capture assay for palmitoylation, Co-IP, single-cell RNA sequencing, Pdgfrα-CreERT conditional mouse model, behavioral tests, iron/ferroptosis markers Journal of advanced research Medium 39929269
2024 CD36 upregulates TfR1 expression in CD8+ T cells via the oxLDL-p38-CEBPB signaling axis in the tumor microenvironment. Depletion of CD36 in CD8+ T cells inhibits TfR1 upregulation and prevents iron accumulation and lipid peroxidation-driven T cell dysfunction. Single-cell RNA sequencing, flow cytometry, CD36 depletion, p38/CEBPB inhibitor studies, intracellular iron and lipid peroxide measurements Clinical and molecular hepatology Medium 40037690
2024 Histone acetyltransferase Kat2a promotes ferroptosis by enhancing H3K27ac and H3K9ac enrichment on the Tfrc (and Hmox1) promoter regions, thereby increasing Tfrc transcription. ALKBH5 demethylase reduces m6A methylation on Kat2a mRNA, and YTHDF2 mediates Kat2a mRNA degradation, providing an upstream regulatory mechanism. Kat2a inhibition in vitro and in vivo, ChIP for H3K27ac/H3K9ac on Tfrc promoter, YTHDF2/ALKBH5 functional studies, ferroptosis assays in DCM model Cell death & disease Medium 38858351
2024 ATF3 (activating transcription factor 3) promotes osteocyte ferroptosis during aging by upregulating TfR1 expression (enhancing iron uptake) while simultaneously inhibiting SLC7A11-mediated cystine import, leading to iron overload and lipid peroxidation. Single-cell transcriptome analysis, ATF3 inhibition in aged mice, ferroptosis markers in cortical bone, TfR1 and SLC7A11 expression analysis Cell proliferation Medium 38764128
2024 HIF-2α upregulates TFR1 expression in cartilage endplate chondrocytes in response to oxidative stress and pro-inflammatory cytokines; excess TFR1-mediated iron accumulation induces ferroptosis and triggers c-GAS/STING-mediated innate immune inflammation via mitochondrial damage and mtDNA release. IDD mouse model, TfR1 siRNA knockdown, HIF-2α pathway analysis, c-GAS/STING inhibition with siRNA and ethidium bromide, western blot/immunofluorescence Journal of orthopaedic translation Medium 38808263
2024 TIMP1 regulates HGHF-induced ferroptosis in osteoblasts by inhibiting TFRC ubiquitination (preventing its proteasomal degradation), thereby increasing TFRC protein levels and promoting iron accumulation. TFRC overexpression reversed the ferroptosis inhibition caused by TIMP1 knockout. TIMP1 knockout and TFRC overexpression in osteoblasts, ubiquitination assays, ferroptosis markers, type 2 diabetic mouse model, western blot/flow cytometry Molecular medicine Medium 39578773
2024 RAB17 attenuates ferroptosis in endometrial cancer cells by inhibiting TFRC protein expression in a ubiquitin proteasome-dependent manner, thereby reducing iron uptake. Under low-glucose conditions, RAB17 expression increases and limits ferroptosis through the RAB17-TFRC axis. RAB17 knockdown/overexpression, TFRC protein stability/ubiquitination assays, ferroptosis phenotyping, xenograft and clinical correlation Cell death & disease Medium 39242574
2023 NUF2 inhibits p62-mediated autophagic degradation of TFR1 via p38/MAPK signaling, thereby stabilizing TFR1 protein and promoting cholangiocarcinoma progression. NUF2 overexpression/knockdown, p62-TFR1 binding assay, p38/MAPK inhibition, autophagic flux measurement, TFR1 protein stability assays International journal of biological sciences Medium 37056930
2023 ANXA10 knockdown induces ferroptosis by inhibiting autophagy-mediated TFRC degradation, leading to increased TFRC protein levels, labile iron accumulation, and lipid peroxidation in colorectal cancer cells. ANXA10 knockdown, TFRC protein stability measurement, autophagy flux assay (SQSTM1 accumulation), ferroptosis markers (Fe2+, MDA, ROS), immunofluorescence Cell death & disease Medium 37666806
2019 TfR1 is identified as the cell-surface target of the aptamer XQ-2d on pancreatic cancer cells. XQ-2d shares the same binding site on CD71 as transferrin (Tf), competitively inhibiting Tf binding, while the anti-CD71 antibody binds at a distinct site approximately 15 nm away as measured by surface energy transfer nanoruler. CD71 knockdown abolishing aptamer binding, competitive binding analysis with Tf and anti-CD71 antibody, surface energy transfer (SET) nanoruler distance measurement, molecular dynamics simulation Journal of the American Chemical Society Medium 31185171
2009 TFRC is an immediate target gene of the canonical Wnt pathway, with Myc and Tfrc expression induced within less than 1 hour of Wnt-3a stimulation in C57MG cells, earlier than other Wnt targets such as Ccnd1. Time-course gene expression analysis after Wnt-3a stimulation, classification of target gene expression chronology Cell biology international Low 19353769
2009 miR-320 targets the transferrin receptor 1 (TfR1/CD71) 3'UTR and suppresses TfR1 surface expression and cell proliferation in HL-60 leukemia cells during monocytic differentiation. miR-320 enforced expression in HL-60 cells, TfR1 surface expression measurement, cell proliferation assay Experimental hematology Low 19135902
2020 TFRC is essential for meiotic progression in mouse spermatocytes; TFRC knockdown via morpholino causes spermatocyte apoptosis, accumulation of leptotene/zygotene spermatocytes, arrest before pachytene, sustained γH2AX association, and SYCP1/SYCP3 dissociation beyond the sex body, indicating roles in DNA double-strand break repair and chromosomal synapsis. TFRC knockdown via morpholino oligonucleotides in neonatal testis culture, chromosomal spread technique, γH2AX/SYCP1/SYCP3 immunostaining, apoptosis assay Zygote Medium 33323153
2024 NAT10-mediated ac4C acetylation of TFRC mRNA stabilizes it, increasing TFRC expression and promoting ferroptosis in lung microvascular endothelial cells during sepsis-induced pulmonary injury. NAT10 inhibition in vitro and in vivo (sepsis rat model), ac4C assay on TFRC mRNA, ferroptosis markers, cell viability assays Molecular medicine Medium 39251905
2023 TFEB promotes TFRC in cardiomyocytes via STAT3, which in turn upregulates Ccl2 expression to recruit and activate macrophages. HIF-1α regulates TFRC expression in cardiomyocytes during heart failure. TAC mouse model, ISO/PHE-stimulated cardiomyocytes, immunofluorescence for TFRC and macrophage infiltration, flow cytometry, STAT3 pathway analysis, HIF-1α manipulation Immunity, inflammation and disease Low 37647427
2019 lncRNA-IUR-5 suppresses Bcr-Abl-mediated tumorigenesis by negatively regulating STAT5-mediated expression of CD71 (TfR1), as demonstrated by RNA pulldown and RNA immunoprecipitation showing lncRNA-IUR-5 interaction with STAT5 pathway components. RNA pulldown, RNA immunoprecipitation (RIP), transcriptome RNA-seq, lncRNA-IUR KD transgenic mice, Bcr-Abl transformation assay Molecular cancer Low 30961617
2024 FTO demethylase activity reduces m6A modification on TfRc mRNA; YTHDF1 binds m6A-modified TfRc mRNA and promotes its translation, while YTHDF2 mediates stability of SLC7A11 mRNA via m6A. Inhibition of AR transcriptional regulation of FTO by BPF exposure dysregulates this axis. ChIP for AR binding to FTO promoter, MeRIP for m6A on TfRc mRNA, RIP for YTHDF1-TfRc mRNA and YTHDF2-SLC7A11 mRNA binding, FTO overexpression Environmental pollution Medium 38996995
2024 Serum iron, transferrin saturation, and hepatic Tfrc expression exhibit circadian rhythms that are maintained in constant darkness and ablated by Bmal1 knockout, demonstrating endogenous circadian control. Hepatic Tfrc expression and erythropoietic activity oscillate in opposing phases. Constant darkness housing, Bmal1 knockout mice, time-series serum iron and TSAT measurement, hepatic Tfrc qPCR, erythropoietic activity assays American journal of hematology Medium 39152780
2023 H3K9me3 (mediated by Suv39h1 methyltransferase) is enriched at the promoter and gene body of Tfr1 and represses its transcription during hemin-induced ferroptosis in neuronal cells. Inhibition of Suv39h1/H3K9me3 aggravates ferroptosis by upregulating Tfr1 expression, demonstrating a protective epigenetic mechanism. ChIP for H3K9me3 at Tfr1 promoter, Suv39h1 siRNA/inhibitor, hemin/RSL3 ferroptosis model, Tfr1 expression analysis, in vivo ICH mouse model with intracerebroventricular Suv39h1 siRNA Journal of cerebral blood flow and metabolism Medium 36960698
2024 TfR1 in CD71+ regulatory T cells (Tregs) is required for Treg perinatal expansion. Treg-restricted CD71 deficiency leads to a scurfy-like autoimmune disease, impaired perinatal Treg proliferation, loss of tissue-Treg gene signature, and hepatic iron overload with increased hepcidin. CD71-null Tregs show decreased proliferation. Treg-specific conditional CD71 knockout mice, Treg proliferation assays, tissue-Treg gene signature analysis, iron metabolism measurements, hepcidin quantification, fecal microbiota analysis JCI insight High 38954474
2024 TfR1 knockdown in neural cells differentiated from Alzheimer's disease patient-derived iPSCs reduces iron overload and mitochondrial dysfunction. TfR1 interacts with GSK3B and promotes GSK3B expression; GSK3B overexpression reverses the protective effects of TfR1 knockdown. TfR1 knockdown/overexpression in AD-iPS differentiated neural cells, co-immunoprecipitation for TfR1-GSK3B interaction, iron/ROS/mitochondrial membrane potential assays, GSK3B rescue experiment European journal of medical research Medium 38321571
2023 Complement C4 directly interacts with TFRC during CVB3 infection (identified by Co-IP and mass spectrometry), and this interaction leads to increased C4b production and decreased downstream complement C3. Regulating the complement C4/C3 pathway via TFRC modulates ferroptosis in CVB3-infected cardiomyocytes. Co-IP and protein mass spectrometry for TFRC-interacting proteins, Fer-1 treatment, complement C3/C4b quantification, functional ferroptosis assays Free radical biology & medicine Medium 38169212

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 LncRNA PVT1 regulates ferroptosis through miR-214-mediated TFR1 and p53. Life sciences 231 32827544
2015 A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency. Nature genetics 223 26642240
2015 Regulation of mitochondrial morphology and function by stearoylation of TFR1. Nature 202 26214738
2021 Antibodies Targeting the Transferrin Receptor 1 (TfR1) as Direct Anti-cancer Agents. Frontiers in immunology 198 33815364
2021 MYCN mediates TFRC-dependent ferroptosis and reveals vulnerabilities in neuroblastoma. Cell death & disease 153 34011924
2022 SPY1 inhibits neuronal ferroptosis in amyotrophic lateral sclerosis by reducing lipid peroxidation through regulation of GCH1 and TFR1. Cell death and differentiation 136 36443440
2019 Elucidation and Structural Modeling of CD71 as a Molecular Target for Cell-Specific Aptamer Binding. Journal of the American Chemical Society 121 31185171
2022 Exosome-Derived lncRNA NEAT1 Exacerbates Sepsis-Associated Encephalopathy by Promoting Ferroptosis Through Regulating miR-9-5p/TFRC and GOT1 Axis. Molecular neurobiology 112 35038133
2022 TFRC upregulation promotes ferroptosis in CVB3 infection via nucleus recruitment of Sp1. Cell death & disease 110 35821227
2009 miR-320 targets transferrin receptor 1 (CD71) and inhibits cell proliferation. Experimental hematology 110 19135902
2021 METTL14 promotes doxorubicin-induced cardiomyocyte ferroptosis by regulating the KCNQ1OT1-miR-7-5p-TFRC axis. Cell biology and toxicology 96 34648132
2023 TFEB regulates cellular labile iron and prevents ferroptosis in a TfR1-dependent manner. Free radical biology & medicine 90 37683766
2020 YTHDF1-enhanced iron metabolism depends on TFRC m6A methylation. Theranostics 85 33204330
2022 Exosomes derived from hepatitis B virus-infected hepatocytes promote liver fibrosis via miR-222/TFRC axis. Cell biology and toxicology 80 34978008
2002 Iron and HFE or TfR1 mutations as comorbid factors for development and progression of chronic hepatitis C. Journal of hepatology 79 12445428
2024 FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC. Nature communications 70 38834654
2024 Inflammation Triggers Chondrocyte Ferroptosis in TMJOA via HIF-1α/TFRC. Journal of dental research 66 38766865
2021 The role of CD71+ erythroid cells in the regulation of the immune response. Pharmacology & therapeutics 66 34171326
2014 Overexpression of transferrin receptor CD71 and its tumorigenic properties in esophageal squamous cell carcinoma. Oncology reports 66 24435655
2023 Stroke by inducing HDAC9-dependent deacetylation of HIF-1 and Sp1, promotes TfR1 transcription and GPX4 reduction, thus determining ferroptotic neuronal death. International journal of biological sciences 64 37324938
2022 Trabectedin induces ferroptosis via regulation of HIF-1α/IRP1/TFR1 and Keap1/Nrf2/GPX4 axis in non-small cell lung cancer cells. Chemico-biological interactions 60 36396105
2017 Decreasing TfR1 expression reverses anemia and hepcidin suppression in β-thalassemic mice. Blood 55 28151426
2021 TRIB2 desensitizes ferroptosis via βTrCP-mediated TFRC ubiquitiantion in liver cancer cells. Cell death discovery 53 34315867
2013 TfR1 interacts with the IKK complex and is involved in IKK-NF-κB signalling. The Biochemical journal 48 23016877
2011 Absence of CD71 transferrin receptor characterizes human gastric adenosquamous carcinoma stem cells. Annals of surgical oncology 48 21523522
2024 Inhibition of METTL3 ameliorates doxorubicin-induced cardiotoxicity through suppression of TFRC-mediated ferroptosis. Redox biology 47 38631119
2020 Estrogen-induced epigenetic silencing of FTH1 and TFRC genes reduces liver cancer cell growth and survival. Epigenetics 47 32476555
2023 The muscle-enriched myokine Musclin impairs beige fat thermogenesis and systemic energy homeostasis via Tfr1/PKA signaling in male mice. Nature communications 46 37468484
2019 Downregulation of TfR1 promotes progression of colorectal cancer via the JAK/STAT pathway. Cancer management and research 46 31372038
2009 Chronological expression of Wnt target genes Ccnd1, Myc, Cdkn1a, Tfrc, Plf1 and Ramp3. Cell biology international 46 19353769
2022 Machine Learning Classifies Ferroptosis and Apoptosis Cell Death Modalities with TfR1 Immunostaining. ACS chemical biology 44 35230809
2024 O-GlcNAcylation regulates the stability of transferrin receptor (TFRC) to control the ferroptosis in hepatocellular carcinoma cells. Redox biology 43 38744192
2022 Hypoxia increases expression of selected blood-brain barrier transporters GLUT-1, P-gp, SLC7A5 and TFRC, while maintaining barrier integrity, in brain capillary endothelial monolayers. Fluids and barriers of the CNS 41 34983574
2022 ESR1 inhibits ionizing radiation-induced ferroptosis in breast cancer cells via the NEDD4L/CD71 pathway. Archives of biochemistry and biophysics 41 35613689
2011 Aberrant expression of TfR1/CD71 in thyroid carcinomas identifies a novel potential diagnostic marker and therapeutic target. Thyroid : official journal of the American Thyroid Association 41 21323588
2024 Histone acetyltransferase Kat2a regulates ferroptosis via enhancing Tfrc and Hmox1 expression in diabetic cardiomyopathy. Cell death & disease 38 38858351
2020 TFRC promotes epithelial ovarian cancer cell proliferation and metastasis via up-regulation of AXIN2 expression. American journal of cancer research 38 32064157
2019 Quantitative Analysis of Transferrin Receptor 1 (TfR1) in Individual Breast Cancer Cells by Means of Labeled Antibodies and Elemental (ICP-MS) Detection. Analytical chemistry 37 31694367
2019 Novel lncRNA-IUR suppresses Bcr-Abl-induced tumorigenesis through regulation of STAT5-CD71 pathway. Molecular cancer 35 30961617
2023 IGF2BP2 promotes colorectal cancer progression by upregulating the expression of TFRC and enhancing iron metabolism. Biology direct 34 37088822
2022 LC3-dependent EV loading and secretion (LDELS) promotes TFRC (transferrin receptor) secretion via extracellular vesicles. Autophagy 34 36286616
2024 METTL3 regulates TFRC ubiquitination and ferroptosis through stabilizing NEDD4L mRNA to impact stroke. Cell biology and toxicology 33 38302612
2023 Regulation of iron homeostasis by hepatocyte TfR1 requires HFE and contributes to hepcidin suppression in β-thalassemia. Blood 33 36322932
2022 Nonclinical Efficacy and Safety of CX-2029, an Anti-CD71 Probody-Drug Conjugate. Molecular cancer therapeutics 33 35666803
2024 Advancing glioblastoma treatment through iron metabolism: A focus on TfR1 and Ferroptosis innovations. International journal of biological macromolecules 31 39153669
2019 Effects of Heterozygous TfR1 (Transferrin Receptor 1) Deletion in Pathogenesis of Renal Fibrosis in Mice. Hypertension (Dallas, Tex. : 1979) 31 31838906
2023 CD71+ erythroid cells suppress T-cell effector functions and predict immunotherapy outcomes in patients with virus-associated solid tumors. Journal for immunotherapy of cancer 30 37236637
2023 Knockdown of TFRC suppressed the progression of nasopharyngeal carcinoma by downregulating the PI3K/Akt/mTOR pathway. Cancer cell international 30 37644594
2023 Cinobufotalin Induces Ferroptosis to Suppress Lung Cancer Cell Growth by lncRNA LINC00597/hsa-miR-367-3p/TFRC Pathway via Resibufogenin. Anti-cancer agents in medicinal chemistry 27 36221890
2023 Knockdown of ANXA10 induces ferroptosis by inhibiting autophagy-mediated TFRC degradation in colorectal cancer. Cell death & disease 27 37666806
2014 Anaplastic Thyroid Carcinoma: Current Treatments and Potential New Therapeutic Options with Emphasis on TfR1/CD71. International journal of endocrinology 26 25097549
2024 Rosmarinic acid liposomes suppress ferroptosis in ischemic brain via inhibition of TfR1 in BMECs. Phytomedicine : international journal of phytotherapy and phytopharmacology 24 38968791
2024 CCT3/ACTN4/TFRC axis protects hepatocellular carcinoma cells from ferroptosis by inhibiting iron endocytosis. Journal of experimental & clinical cancer research : CR 24 39210442
2023 Nutrition impact on ILC3 maintenance and function centers on a cell-intrinsic CD71-iron axis. Nature immunology 24 37709985
2020 Clinical and Immunological Characterization of Combined Immunodeficiency Due to TFRC Mutation in Eight Patients. Journal of clinical immunology 24 32851577
2024 HIF-2α/TFR1 mediated iron homeostasis disruption aggravates cartilage endplate degeneration through ferroptotic damage and mtDNA release: A new mechanism of intervertebral disc degeneration. Journal of orthopaedic translation 22 38808263
2019 Erythroid-Progenitor-Targeted Gene Therapy Using Bifunctional TFR1 Ligand-Peptides in Human Erythropoietic Protoporphyria. American journal of human genetics 22 30712775
2004 Differential expression and function of IgA receptors (CD89 and CD71) during maturation of dendritic cells. Journal of leukocyte biology 22 15371488
2025 CD36 promotes iron accumulation and dysfunction in CD8+ T cells via the p38-CEBPB-TfR1 axis in early-stage hepatocellular carcinoma. Clinical and molecular hepatology 21 40037690
2024 TfR1 mediated iron metabolism dysfunction as a potential therapeutic target for osteoarthritis. Arthritis research & therapy 21 38493104
2020 Rational design of universal immunotherapy for TfR1-tropic arenaviruses. Nature communications 21 31900422
2016 Evaluating the effectiveness of transferrin receptor-1 (TfR1) as a magnetic resonance reporter gene. Contrast media & molecular imaging 21 26929139
2024 Osteocyte ferroptosis induced by ATF3/TFR1 contributes to cortical bone loss during ageing. Cell proliferation 20 38764128
2023 NUF2 Drives Cholangiocarcinoma Progression and Migration via Inhibiting Autophagic Degradation of TFR1. International journal of biological sciences 20 37056930
2023 Anaplastic thyroid cancer cells reduce CD71 levels to increase iron overload tolerance. Journal of translational medicine 20 37924062
2022 Identification of Transferrin Receptor 1 (TfR1) Overexpressed in Lung Cancer Cells, and Internalization of Magnetic Au-CoFe2O4 Core-Shell Nanoparticles Functionalized with Its Ligand in a Cellular Model of Small Cell Lung Cancer (SCLC). Pharmaceutics 20 36015341
2002 Transferrin receptor 1 (TfR1) and putative stimulator of Fe transport (SFT) expression in iron deficiency and overload: an overview. Blood cells, molecules & diseases 20 12547240
2022 Artesunate, a new antimalarial clinical drug, exhibits potent anti-AML activity by targeting the ROS/Bim and TFRC/Fe2+ pathways. British journal of pharmacology 19 36368726
2024 TFR1-Mediated Iron Metabolism Orchestrates Tumor Ferroptosis and Immunity in Non-Small Cell Lung Cancer. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer 18 38505909
2023 H3K9 trimethylation dictates neuronal ferroptosis through repressing Tfr1. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 18 36960698
2024 TFR1 knockdown alleviates iron overload and mitochondrial dysfunction during neural differentiation of Alzheimer's disease-derived induced pluripotent stem cells by interacting with GSK3B. European journal of medical research 17 38321571
2024 Expression of transferrin receptor/TFRC protein in bladder cancer cell T24 and its role in inducing iron death in bladder cancer. International journal of biological macromolecules 17 38908617
2024 FTO mediates bisphenol F-induced blood-testis barrier impairment through regulating ferroptosis via YTHDF1/TfRc and YTHDF2/SLC7A11 signal axis. Environmental pollution (Barking, Essex : 1987) 16 38996995
2024 NAT10-mediated ac4C acetylation of TFRC promotes sepsis-induced pulmonary injury through regulating ferroptosis. Molecular medicine (Cambridge, Mass.) 16 39251905
2023 NSD2 promotes pressure overload-induced cardiac hypertrophy via activating circCmiss1/TfR1/ferroptosis signaling. Life sciences 16 37352916
2023 Manganese-induced miR-125b-2-3p promotes anxiety-like behavior via TFR1-mediated ferroptosis. Environmental pollution (Barking, Essex : 1987) 16 38159631
2020 Transferrin receptor (TFRC) is essential for meiotic progression during mouse spermatogenesis. Zygote (Cambridge, England) 16 33323153
2020 TfR1 Extensively Regulates the Expression of Genes Associated with Ion Transport and Immunity. Current medical science 15 32681254
2020 CD71 mesangial IgA1 receptor and the progression of IgA nephropathy. Translational research : the journal of laboratory and clinical medicine 15 33122053
2023 Complement components regulates ferroptosis in CVB3 viral myocarditis by interatction with TFRC. Free radical biology & medicine 14 38169212
2021 Proteomics study of colorectal cancer and adenomatous polyps identifies TFR1, SAHH, and HV307 as potential biomarkers for screening. Journal of proteomics 14 33915303
2020 Structure prediction of transferrin receptor protein 1 (TfR1) by homology modelling, docking, and molecular dynamics simulation studies. Heliyon 14 32021925
2019 CD71+ Population Enriched by HPV-E6 Protein Promotes Cancer Aggressiveness and Radioresistance in Cervical Cancer Cells. Molecular cancer research : MCR 14 31235657
2012 Cytometric evaluation of transferrin receptor 1 (CD71) in childhood acute lymphoblastic leukemia. Folia histochemica et cytobiologica 14 22763969
2024 Serum iron and transferrin saturation variation are circadian regulated and linked to the harmonic circadian oscillations of erythropoiesis and hepatic Tfrc expression in mice. American journal of hematology 13 39152780
2023 TFRC in cardiomyocytes promotes macrophage infiltration and activation during the process of heart failure through regulating Ccl2 expression mediated by hypoxia inducible factor-1α. Immunity, inflammation and disease 13 37647427
2022 Identification and Characterization of Elevated Expression of Transferrin and Its Receptor TfR1 in Mouse Models of Depression. Brain sciences 13 36291201
2005 Expression of Duffy antigen receptor for chemokines during reticulocyte maturation: using a CD71 flow cytometric technique to identify reticulocytes. Immunohematology 13 15783301
2024 A Novel Homozygous Germline Mutation in Transferrin Receptor 1 (TfR1) Leads to Combined Immunodeficiency and Provides New Insights into Iron-Immunity Axis. Journal of clinical immunology 12 38270687
2022 Identification of a Novel Inhibitor of TfR1 from Designed and Synthesized Muriceidine A Derivatives. Antioxidants (Basel, Switzerland) 12 35624697
2021 LncRNA RP1-86C11.7 exacerbates the glioma progression and oncogenicity by hsa-miR-144-3p/TFRC signaling. Translational oncology 12 34571345
2020 Expression of transferrin receptor-1 (TFR-1) in canine osteosarcomas. Veterinary medicine and science 12 32239803
2025 Neonatal sevoflurane exposures inhibits DHHC5-mediated palmitoylation of TfR1 in oligodendrocytes, leading to hypomyelination and neurological impairments. Journal of advanced research 11 39929269
2024 Iron capture through CD71 drives perinatal and tumor-associated Treg expansion. JCI insight 11 38954474
2024 RAB17 promotes endometrial cancer progression by inhibiting TFRC-dependent ferroptosis. Cell death & disease 11 39242574
2025 Circular RNA TFRC/SCD1 mRNA interaction regulates ferroptosis and metastasis in gastric cancer. Cell death & disease 10 40473597
2021 LncRNA LINC00888 upregulation predicts a worse survival of laryngeal cancer patients and accelerates the growth and mobility of laryngeal cancer cells through regulation of miR-378g/TFRC. Journal of biochemical and molecular toxicology 10 34472153
2024 circ-TFRC downregulation suppresses ovarian cancer progression via miR-615-3p/IGF2 axis regulation. Cancer cell international 9 38678242
2024 TIMP1 regulates ferroptosis in osteoblasts by inhibiting TFRC ubiquitination: an in vitro and in vivo study. Molecular medicine (Cambridge, Mass.) 9 39578773
2022 TFR1 expression in induced sputum is associated with asthma severity. PeerJ 9 35602900

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