Affinage

ID3

DNA-binding protein inhibitor ID-3 · UniProt Q02535

Length
119 aa
Mass
13.0 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ID3 is a dominant-negative helix-loop-helix (HLH) protein that controls the balance between proliferation and differentiation across many lineages by sequestering E-protein transcription factors and blocking their binding to E-box DNA elements (PMID:8139914, PMID:8759016). Lacking its own basic DNA-binding region, ID3 forms heterodimers with bHLH proteins including E12, E47, E2-2 and MyoD, preferentially targeting E2A-class factors and inhibiting both their DNA binding and transcriptional activity (PMID:8139914, PMID:8759016, PMID:9525934). Through this antagonism ID3 drives cell-cycle progression and represses differentiation: it promotes S-phase entry, opposes muscle, adipocyte and erythroid differentiation programs (PMID:8853902, PMID:9121427, PMID:9525934), and transcriptionally represses the CDK inhibitors p21 and p27 — the latter through inhibition of ELK1 at the p27 promoter — thereby promoting Rb hyperphosphorylation (PMID:12021231, PMID:17404577). ID3 activity is gated by signaling and post-translational control: cyclin E/A–Cdk2 phosphorylates ID3 at Ser5 to nullify its G1 function and shift its bHLH target specificity (PMID:9372912), and ID3 is turned over by ubiquitin-dependent proteasomal degradation involving the COP9 signalosome subunits CSN5/CSN7 (PMID:15451666). ID3 transcription is induced by Ras–ERK MAPK signaling downstream of antigen receptors (PMID:11175815), by TGF-β and BMP–SMAD signaling (PMID:11224524, PMID:15121845, PMID:21056086), and directly by Pax7, Wnt/β-catenin and BMP2 at defined promoter elements (PMID:19458195, PMID:21056086, PMID:30520117). In the immune system ID3 enforces naive, memory and regulatory T-cell fates by restraining E2A/E2-2 activity, governing thymocyte selection, αβ/γδ lineage choice, Treg Foxp3 maintenance, germinal-center B-cell differentiation and stem-like memory CD8 T-cell programs (PMID:10661402, PMID:19833086, PMID:21857655, PMID:24973820, PMID:27217539, PMID:39888981). Beyond transcription, ATM phosphorylates ID3 at Ser65 following DNA double-strand breaks to enable direct interaction with MDC1, promoting MDC1 foci formation and double-strand-break repair (PMID:29026069). ID3 also determines Kupffer-cell anti-tumor phagocytic activity by buffering ELK1 and E2A occupancy at the SIRPA locus (PMID:38326607), and is recurrently inactivated by somatic mutation in Burkitt lymphoma, establishing it as a tumor suppressor in that disease (PMID:23143595).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1994 High

    Established the fundamental biochemical mechanism: how a protein lacking a DNA-binding domain could regulate transcription, by showing ID3 acts as a dominant-negative dimerization partner.

    Evidence In vitro DNA-binding inhibition and heterodimer formation assays with E47 and MyoD

    PMID:8139914

    Open questions at the time
    • Did not define which E-proteins are physiologically targeted in vivo
    • No structural basis for dimerization specificity
  2. 1996 High

    Defined ID3's interaction partner repertoire and target preference, showing it selectively engages E2A-class factors over c-Myc and that both HLH and C-terminal domains are required for dominant-negative differentiation block.

    Evidence Yeast two-hybrid, co-immunoprecipitation, reporter assays, and domain mutagenesis in muscle cells

    PMID:8759016 PMID:8853902 PMID:8853903

    Open questions at the time
    • C-terminal domain mechanism not molecularly defined
    • In vitro target preference not validated genome-wide
  3. 1997 High

    Resolved how ID3 activity is temporally controlled within the cell cycle by identifying Cdk2 phosphorylation at Ser5 as a switch that nullifies its G1 function and alters bHLH target specificity.

    Evidence In vitro kinase assays, Ser5→Asp/Ala mutagenesis, E-box reporter and S-phase entry assays

    PMID:9372912

    Open questions at the time
    • In vivo kinetics of phosphorylation cycling not established
    • How phosphorylation alters target selectivity mechanistically unresolved
  4. 1997 Medium

    Generalized the anti-differentiation role beyond muscle, showing ID3 blocks adipogenesis and is transcriptionally downregulated during differentiation.

    Evidence Stable ID3 overexpression and transcription-rate analysis in preadipocytes

    PMID:9121427

    Open questions at the time
    • E-protein target in adipogenesis not yet identified (later resolved as E47/adiponectin)
  5. 1999 High

    Genetic knockouts established ID3's non-redundant, lineage-specific roles in lymphocyte signaling, thymocyte selection, and neural/endothelial development, placing it in the E2A pathway in vivo.

    Evidence Id3 single and Id1/Id3 double knockout mice with proliferation, selection, neural marker and xenograft vascularization assays

    PMID:10454544 PMID:10537105 PMID:10661402

    Open questions at the time
    • Functional redundancy among Id family members complicates single-gene interpretation
    • Direct E2A target genes downstream not yet mapped
  6. 2001 High

    Connected upstream signaling to ID3, showing Ras–ERK MAPK downstream of TCR and TGF-β control ID3 transcription, linking extracellular cues to E-protein activity.

    Evidence Primary thymocyte stimulation with ERK inhibition; TGF-β stimulation in knockout B-cell progenitors

    PMID:11175815 PMID:11224524

    Open questions at the time
    • Transcription factors directly driving ID3 induction not pinpointed in these studies
  7. 2001 Medium

    Revealed isoform-level functional diversification: an intron-retaining Id3a isoform with a distinct C-terminus that is pro-apoptotic rather than pro-proliferative in vascular smooth muscle.

    Evidence RT-PCR cloning, adenoviral overexpression, and balloon-injury carotid model

    PMID:11348870 PMID:15159391

    Open questions at the time
    • Regulation of the splicing switch not defined
    • Human relevance of the isoform unclear
  8. 2002 Medium

    Established the downstream cell-cycle output of ID3 in vascular cells, repressing p21, p27 and p53 and driving Rb hyperphosphorylation, with KLF4 identified as an upstream repressor.

    Evidence Antisense/sense transfection, Western blotting for cell-cycle regulators, and promoter binding analysis in VSMCs

    PMID:12021231 PMID:12087069

    Open questions at the time
    • Whether p21/p27 repression is direct or E-protein-mediated not resolved here
    • Single lab
  9. 2004 High

    Defined ID3 protein turnover, showing COP9 signalosome–dependent ubiquitin-proteasome degradation via CSN5/CSN7 interaction, providing a post-translational layer of regulation.

    Evidence Mammalian two-hybrid, pull-down, far Western, in vitro kinase and ubiquitin co-transfection assays

    PMID:15451666

    Open questions at the time
    • E3 ligase mediating ID3 ubiquitination not identified
    • Physiological signals triggering degradation unclear
  10. 2004 High

    Positioned ID3 as a TGF-β/BMP signaling node controlling EMT and growth inhibition, and resolved direct E-box target mechanisms at the SRG3 promoter underlying glucocorticoid sensitivity.

    Evidence cDNA microarray, reciprocal overexpression/knockdown, EMSA and promoter reporters in epithelial cells and thymocytes

    PMID:15016815 PMID:15121845

    Open questions at the time
    • Promoter-specific selectivity of E-protein targeting not generalized
    • EMT effector genes downstream not mapped
  11. 2004 High

    Extended ID3's role to autoimmunity and viral oncogenesis, showing a T-cell-intrinsic protective function against Sjögren-like disease and EBV-LMP1 induction of ID3.

    Evidence Adoptive transfer and thymectomy in Id3 knockout mice; expression arrays in LMP1-transformed cells

    PMID:15485632 PMID:15564458

    Open questions at the time
    • Identity of the autoreactive T-cell-driving E-protein target unresolved
    • LMP1→ID3 functional consequence inferred from correlation
  12. 2007 High

    Defined the direct transcriptional mechanism of cell-cycle control, showing ID3 represses p27 via inhibition of ELK1 at the p27 promoter to drive G1/S progression.

    Evidence siRNA knockdown, qRT-PCR, promoter reporter, ChIP and cell-cycle analysis

    PMID:17404577

    Open questions at the time
    • How ID3 inhibits ELK1 mechanistically (direct binding vs. indirect) not fully resolved
  13. 2008 High

    Provided definitive in vivo and in vitro evidence for the E-box displacement mechanism in adipogenesis, showing ID3 blocks E47 binding to the adiponectin promoter.

    Evidence ChIP in differentiating adipocytes and Id3-null tissue, promoter reporter with E-box mutation

    PMID:18669923

    Open questions at the time
    • Metabolic phenotype of altered adiponectin in vivo not fully characterized
  14. 2009 High

    Established ID3 as a determinant of T-lineage fate, being induced by ERK–Egr signaling and necessary and sufficient for γδ effector differentiation independent of Notch.

    Evidence Id3 knockout and retroviral overexpression with Notch inhibition and cytokine assays

    PMID:19833086

    Open questions at the time
    • E-protein targets specifying γδ effector program not detailed
  15. 2010 Medium

    Dissected the BMP2→SMAD transcriptional control of ID3, identifying distinct proximal and distal cis-regulatory elements.

    Evidence Promoter-reporter dissection with mutagenesis, receptor and SMAD overexpression and RNAi

    PMID:21056086

    Open questions at the time
    • Identity of the protein complex binding the novel proximal element not determined
  16. 2011 High

    Identified ID3 as a master regulator of CD8 T-cell memory versus effector fate, repressed by Blimp-1 in short-lived effectors and marking long-lived memory precursors.

    Evidence ChIP, retroviral enforced expression, and Id3 reporter/knockout mice with memory population analysis

    PMID:21857655 PMID:22057288 PMID:22057289

    Open questions at the time
    • Downstream genome-stability genes mediating memory persistence only partially defined
  17. 2012 High

    Established ID3 as a context-dependent cancer regulator: a self-renewal/genome-protection factor in colon and glioma stem cells, and a recurrently inactivated tumor suppressor in Burkitt lymphoma.

    Evidence siRNA silencing with serial transplantation and invasion assays; whole-genome/exome sequencing of Burkitt lymphoma cohorts

    PMID:22698403 PMID:23022473 PMID:23143595

    Open questions at the time
    • Opposing oncogenic vs. tumor-suppressive roles across tissues not mechanistically reconciled
    • Functional impact of specific Burkitt mutations on E-protein binding not assayed
  18. 2012 Medium

    Extended ID3's vascular role to atheroprotection, governing B-cell aortic homing via CCR6 and VSMC VCAM-1 expression via E12 antagonism.

    Evidence Id3 knockout in Apoe-/- and Ldlr-/- mice, adoptive transfer, ChIP and atherosclerosis quantification

    PMID:22034493 PMID:23042815

    Open questions at the time
    • Mechanism linking ID3 to CCR6 transcription not fully defined
    • Single lab
  19. 2014 High

    Defined ID2/ID3 as required for regulatory and follicular regulatory T-cell homeostasis, with TCR signaling lowering ID3 to enable the TFR program.

    Evidence Conditional Id2/Id3 knockout in Treg cells with transcriptional profiling and adoptive transfer

    PMID:24973820

    Open questions at the time
    • Quantitative threshold of ID3 dosage governing the switch not defined
  20. 2015 High

    Resolved how cytokine signaling tunes ID3 to control TH9 differentiation, identifying a TAK1–Id3–E2A/GATA-3 axis at the Il9 promoter.

    Evidence Id3 knockout, TAK1 inhibition, ChIP at Il9 promoter and IL-9 production in a melanoma model

    PMID:26322481

    Open questions at the time
    • Direct E2A/GATA-3 cooperation mechanism at Il9 not fully resolved
  21. 2015 High

    Established reciprocal ID3–E47 control of neural stem cell astrocyte differentiation downstream of BMP-2 injury signaling.

    Evidence Reciprocal Id3 and E47 knockout in NSPCs with cortical injury and differentiation assays

    PMID:26438726

    Open questions at the time
    • Astrocyte-specific genes repressed by E47 not enumerated
  22. 2016 High

    Defined the requirement for ID3 downregulation to release E2A/E2-2 for germinal-center B-cell and plasma-cell differentiation, and ID3 maintenance of Treg Foxp3 stability via E47–Spi-B/SOCS3.

    Evidence Id3 knockout B-cell differentiation assays; conditional Id3 KO and E47 overexpression in Treg cells

    PMID:27217539 PMID:27974197

    Open questions at the time
    • Redundancy of E2A and E2-2 not quantitatively partitioned
    • Treg Foxp3 mechanism single lab
  23. 2017 High

    Uncovered a transcription-independent function: ATM-phosphorylated ID3 (Ser65) directly binds MDC1 to promote DNA double-strand-break repair, expanding ID3 biology beyond E-protein antagonism.

    Evidence Co-IP, ATM kinase assay, phospho-mutant analysis, MDC1 foci imaging, comet and clonogenic survival assays

    PMID:29026069

    Open questions at the time
    • How ID3 mechanistically stabilizes MDC1 at breaks unresolved
    • Relationship to ID3 transcriptional roles unclear
  24. 2017 Medium

    Linked Wnt/β-catenin and ANGPTL4 signaling to ID3 induction, with ID3 then engaging scleraxis to limit fibrotic collagen production.

    Evidence Co-IP, nuclear β-catenin fractionation, Id3 reporter, siRNA and collagen assays in fibroblasts

    PMID:28740178

    Open questions at the time
    • Direct ID3–scleraxis structural interaction not characterized
    • Single lab
  25. 2018 Medium

    Placed ID3 downstream of CD5L-induced autophagy in M2 macrophage polarization.

    Evidence siRNA epistasis (ATG7→ID3→polarization) with LC3-II and flow cytometry readouts

    PMID:29593730

    Open questions at the time
    • Mechanism by which autophagy induces ID3 transcription unknown
    • Single lab
  26. 2019 Medium

    Showed ID3 promotes cancer stemness by blocking E47 recruitment to the β-catenin promoter, activating Wnt signaling in cholangiocarcinoma.

    Evidence Co-IP, ChIP, ID3 overexpression/knockdown, Wnt reporter and xenograft

    PMID:30520117

    Open questions at the time
    • Reciprocity with prior β-catenin→ID3 induction model not reconciled
    • Single lab
  27. 2024 High

    Established ID3 as the Kupffer-cell lineage-determining factor controlling macrophage anti-tumor activity by buffering ELK1/E2A occupancy at the SIRPA locus.

    Evidence Reciprocal loss/gain-of-function in mouse and human iPSC-derived macrophages, ChIP at SIRPA, and phagocytosis assays

    PMID:38326607

    Open questions at the time
    • How ID3 dosage sets the inhibitory/activating receptor balance quantitatively unresolved
  28. 2025 High

    Defined ID3 as a marker and requirement of stem-like/Tpex CD8 T-cell progenitors essential for durable anti-tumor and anti-chronic-infection immunity, inducible by IL-1 family cytokines.

    Evidence Id3 knockout and reporter mice, adoptive transfer in chronic infection and tumor models, cytokine stimulation

    PMID:39888981

    Open questions at the time
    • Transcriptional targets of ID3 sustaining the Tpex state not enumerated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ID3's transcription-independent DNA-repair role integrates with its dominant E-protein-antagonist function, and what reconciles its opposing oncogenic versus tumor-suppressive roles across tissues, remain open.
  • No structural model of ID3–MDC1 versus ID3–E-protein interaction surfaces
  • E3 ligase and full degradation machinery undefined
  • Context-determinants of oncogenic vs. tumor-suppressive function unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0098772 molecular function regulator activity 6 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-168256 Immune System 10 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1640170 Cell Cycle 4 R-HSA-1643685 Disease 3 R-HSA-73894 DNA Repair 1
Partners
CSN5E12E2-2E2AE47ELK1MDC1MYOD

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 ID3 protein contains a HLH dimerization domain but lacks a basic DNA-binding region; it forms heterodimers with bHLH proteins (E47 homodimers and E47/MyoD heterodimers) and inhibits their DNA-binding activity, functioning as a dominant-negative HLH protein. In vitro DNA-binding inhibition assay; heterodimer formation assay Nucleic acids research High 8139914
1996 ID3 interacts with E12, E47, ALF1, and Id4 (all HLH proteins) as identified by yeast two-hybrid and confirmed by co-immunoprecipitation; ID3 disrupts DNA binding by these proteins in vitro and blocks transcriptional activation in cultured cells. ID3 preferentially targets E2A-class transcription factors and shows evidence of interacting with E2-2 and MyoD but not c-Myc. Yeast two-hybrid screen; co-immunoprecipitation; in vitro DNA-binding disruption assay; transcriptional reporter assay in cultured cells Nucleic acids research High 8759016
1996 Stable overexpression of ID3 inhibits differentiation of Sol 8 muscle cells, and both the HLH and C-terminal domains of ID3 are necessary and sufficient for this dominant-negative activity. Overexpression reduces DNA-binding activity in nuclear extracts. Stable transfection; domain mutagenesis; nuclear extract DNA-binding assay; in situ hybridization Cell growth & differentiation High 8853903
1996 Ectopic ID3 expression in C2C12 myoblasts impairs differentiation and promotes S-phase entry; antisense blockade of ID3 potentiates differentiation and cell cycle exit, establishing ID3 as a negative regulator of differentiation that integrates mitogenic signaling into cell cycle progression. Stable and inducible transfection; antisense knockdown; cell cycle analysis Cell growth & differentiation Medium 8853902
1997 Cyclin E–Cdk2 and cyclin A–Cdk2 phosphorylate ID3 at a conserved serine residue (Ser5) during late G1-to-S phase transition. A phosphomimetic ID3 Asp5 mutant cannot promote S-phase entry and loses ability to abrogate E-box-dependent bHLH complex formation in vitro and in vivo, whereas a non-phosphorylatable Ala5 mutant has enhanced activity. Cdk2 phosphorylation thus acts as a switch that nullifies ID3's G1 cell-cycle function and modulates its bHLH target specificity. In vitro kinase assay; site-directed mutagenesis (Ser5→Asp5 and Ser5→Ala5); E-box reporter assay; cell cycle S-phase entry assay in transfected fibroblasts Molecular and cellular biology High 9372912
1997 ID3 prevents adipose differentiation of 3T3-F442A preadipose cells; stably transformed cells expressing ID3 under a viral promoter are virtually unable to differentiate, and ID3 mRNA is actively transcribed in preadipose cells but shows reduced transcription during adipogenesis. Stable transfection with constitutive ID3 expression; transcription rate analysis; differentiation assay Molecular and cellular biology Medium 9121427
1998 ID3 selectively targets the E2A protein E47 in vivo, as demonstrated by a Gal4-VP16 two-hybrid competition assay; ID3 expression in K562 erythroid progenitors promotes erythroid differentiation correlated with a qualitative shift in TAL1/E-protein heterodimer binding profile at E-box sequences. Gal4-VP16 two-hybrid competition assay; E-box-dependent reporter assay; ectopic expression in K562 cells; electrophoretic mobility shift assay The Journal of biological chemistry Medium 9525934
1999 Id3 knockout mice show compromised B-cell proliferative response to BCR cross-linking (but not to LPS), reduced humoral immunity, and defects in cytokine production and isotype switching. The proliferation defect is rescued by ectopic Id1 expression, demonstrating a specific, non-redundant role for ID3 in BCR-to-cell-cycle signaling. Gene knockout mouse; B-cell proliferation assay; rescue by ectopic Id1 expression; immunoglobulin quantification Molecular and cellular biology High 10454544
1999 Id3 null mutant mice display defects in MHC class I- and class II-restricted thymocyte positive selection and impaired H-Y TCR-mediated negative selection. Genetic interaction between E2A and Id3 regulates thymocyte development, placing Id3 in the E2A pathway at the thymocyte selection checkpoint. Id3 knockout mouse; thymocyte selection assay; E2A/Id3 double-mutant epistasis Immunity High 10661402
1999 Id1/Id3 double knockout mice exhibit premature withdrawal of neuroblasts from the cell cycle, expression of neural differentiation markers, vascular malformations in the forebrain, and failure to support tumor xenograft vascularization, demonstrating that Id1 and Id3 are required to maintain neuronal differentiation timing and endothelial cell invasiveness. Double gene knockout mouse; BrdU labeling; neural marker immunostaining; tumor xenograft assay Nature High 10537105
2000 Ectopic expression of ID3 (and ID2) in CD34+ hematopoietic progenitors strongly inhibits development into CD123hi DC2 precursors but does not affect DC1 development, NK cell development, or T and B cell development (which are blocked at later stages), supporting a common lymphoid origin for DC2 precursors. Retroviral ectopic expression in CD34+ progenitors; fetal thymic organ culture; flow cytometry The Journal of experimental medicine Medium 11120774
2001 ID3 transcription is rapidly induced by TCR ligation in primary immature thymocytes, and this induction is regulated in a dose-dependent manner by the ERK MAPK module downstream of TCR signaling, directly connecting the Ras–ERK MAPK cascade to HLH protein activity and E2A DNA binding. Primary thymocyte stimulation; mRNA induction kinetics; ERK pathway inhibition; E2A DNA-binding assay Nature immunology High 11175815
2001 ID3 is induced by TGF-β in B lymphocyte progenitors and mediates TGF-β-induced apoptosis and growth arrest; in the absence of ID3, the apoptotic/growth-arrest response of lymphocyte progenitors to TGF-β is perturbed, identifying E proteins (whose activity is antagonized by ID3) as critical for lymphocyte survival. Id3 knockout mouse; TGF-β stimulation; apoptosis and proliferation assays in lymphocyte progenitors Nature immunology High 11224524
2002 ID3 is a novel redox-sensitive gene induced by superoxide (via angiotensin II or xanthine/xanthine oxidase) in vascular smooth muscle cells. ID3 promotes VSMC proliferation by downregulating p21WAF1/Cip1, p27Kip1, and p53, and causes retinoblastoma protein hyperphosphorylation; antisense ID3 abolishes Ang II–induced proliferation. Differential display; antisense and sense transfection; superoxide dismutase inhibition; Western blot for cell-cycle regulators; DNA synthesis/BrdU assay Circulation Medium 12021231
2002 GKLF (KLF4) binds to the Id3 promoter and transcriptionally represses Id3 expression, while Id3 reciprocally depresses expression of p21WAF1/Cip1, p27KIP1, and p53, establishing a GKLF–ID3 axis controlling redox-sensitive VSMC proliferation. Transfection with GKLF and antisense Id3; promoter binding analysis; gene expression assays; vascular injury mouse model FASEB journal Medium 12087069
2004 TGF-β1 causes long-term repression of ID2 and ID3, while BMP-7 induces sustained ID2/ID3 expression. Ectopic ID3 expression renders epithelial cells refractory to TGF-β-induced growth inhibition and epithelial-mesenchymal transition (EMT), phenocopying the BMP response. Knockdown of ID3 sensitizes cells to BMP-induced growth inhibition and transdifferentiation. cDNA microarray; ectopic overexpression; siRNA knockdown; growth inhibition assay; EMT morphology assessment; Smad4-deficient cells Molecular and cellular biology High 15121845
2004 ID3 has a T-cell intrinsic role in preventing autoimmune Sjögren's syndrome. Adoptive transfer of Id3-deficient T cells into wild-type recipients recapitulates disease symptoms (dry eyes/mouth, lymphocyte infiltration), and neonatal thymectomy or genetic T-cell ablation rescues disease in Id3 KO mice, indicating that abnormal T cells generated during thymic development drive the autoimmune phenotype. Id3 knockout mouse; adoptive transfer; neonatal thymectomy; T-cell ablation Immunity High 15485632
2004 ID3 (and ID1) undergo ubiquitin-dependent proteasomal degradation mediated by the COP9 signalosome (CSN). ID3 physically interacts with CSN subunits CSN5 and CSN7 (demonstrated by pull-down and far Western). Recombinant ID3 is not phosphorylated by CSN-associated kinases CK2 and PKD, but inhibits c-Jun and CSN2 phosphorylation by CK2. Inhibition of CSN-associated kinases by curcumin or emodin increases ID3 ubiquitination and degradation. Overexpression of CSN2 stabilizes ID3 protein. Mammalian two-hybrid; pull-down; far Western; in vitro kinase assay; co-transfection with His-ubiquitin; proteasome inhibitor treatment; His-pull-down for ubiquitin conjugates Journal of molecular biology High 15451666
2004 Latent membrane protein 1 (LMP1) of Epstein-Barr virus induces ID1 and ID3 expression via NF-κB and MAPK signaling; ID3 induction correlates with downregulation of p27Kip1, increased Cdk2 levels, and retinoblastoma protein hyperphosphorylation in LMP1-transformed cells. Genomic expression array; mRNA and protein validation; stable LMP1 expression in C33A and Rat-1 cells Journal of virology Medium 15564458
2004 E2A/HEB heterodimers bind an E-box element in the SRG3 promoter to activate its transcription, and ID3 (induced by TCR→MEK/ERK) represses SRG3 by blocking this E-box binding. Enforced ID3 expression confers glucocorticoid resistance in thymocytes; overexpression of SRG3 overcomes ID3-mediated glucocorticoid resistance. Promoter-reporter assay; electrophoretic mobility shift assay (EMSA); retroviral transduction of Id3; SRG3 overexpression rescue The Journal of biological chemistry Medium 15016815
2004 Id3 is a direct transcriptional target of Pax7 in quiescent satellite cells; chromatin immunoprecipitation shows Pax7 binding upstream of the Id3 promoter in quiescent satellite cells, a conserved Pax7-binding site is required for maximal promoter activation, and shRNA knockdown of Pax7 coordinately reduces Id2 and Id3 expression. Chromatin immunoprecipitation (ChIP); luciferase reporter assay with mutagenesis of Pax7 binding site; shRNA knockdown; ectopic Pax7 expression Molecular biology of the cell High 19458195
2001 Vascular injury induces expression of a novel ID3 isoform (Id3a/Id3L) generated by alternative splicing retaining a 115-bp coding intron that encodes a unique 29-amino acid C-terminus. Unlike canonical ID3, Id3a does not promote SMC growth but instead stimulates apoptosis and inhibits neointimal lesion formation in vivo. Yeast two-hybrid cloning from SMC library; RT-PCR; adenoviral overexpression in SMCs; balloon injury rat carotid model; DNA fragmentation assay Arteriosclerosis, thrombosis, and vascular biology Medium 11348870
2004 The intron-retaining Id3a isoform fails to promote SMC S-phase entry or inhibit p21Cip1 transcription (unlike canonical Id3), but instead stimulates apoptosis and inhibits vascular lesion formation; adenoviral delivery of Id3a inhibits lesion formation in balloon-injured rat carotid arteries in vivo, defining a feedback loop via regulated intron retention. Adenoviral gene transfer; BrdU S-phase assay; p21 promoter reporter; in vivo balloon injury carotid model; Id3a-specific antibody The Journal of biological chemistry Medium 15159391
2007 Id3 regulates p27kip1 mRNA levels in early G1 phase through transcriptional repression via ELK1 inhibition. Id3 silencing prevents p27 mRNA downregulation, blocks G1 progression (inhibits pRb phosphorylation and p130 degradation), and inhibits G1/S transition (blocks cyclin A induction). ChIP confirms Id3-mediated repression through ELK1 at the p27 promoter. siRNA knockdown; quantitative RT-PCR; promoter-reporter assay; chromatin immunoprecipitation (ChIP); cell cycle analysis Oncogene High 17404577
2008 ID3 inhibits E47-mediated and SREBP-1c-mediated adiponectin promoter activation in a dose-dependent manner by interacting with E47 and preventing its binding to a consensus E-box in the adiponectin promoter. ChIP demonstrates E47 binding to the endogenous adiponectin promoter in differentiating adipocytes, which is abolished by ID3 overexpression and enhanced in Id3-null adipose tissue. Luciferase promoter assay; chromatin immunoprecipitation (ChIP); Id3 knockout mouse; ectopic overexpression; E-box mutation Circulation research High 18669923
2009 The ERK–Egr–Id3 pathway plays a defining role in αβ vs. γδ T lineage fate specification: Id3 is markedly induced by γδTCR signaling and is necessary and sufficient to enable γδ-lineage cells to differentiate independently of Notch signaling and become competent IFN-γ-producing effectors. Id3 knockout mouse; retroviral Id3 overexpression; Notch inhibition; cytokine production assay; ERK pathway analysis Immunity High 19833086
2011 Blimp-1 binds to and represses the Id3 promoter in short-lived effector CD8+ T cells (SLECs); repression of Id3 by Blimp-1 limits SLEC persistence as memory cells. Enforced Id3 expression restores SLEC survival and enhances recall responses. ID3 function in this context is mediated in part through inhibition of E2A transcriptional activity and induction of genes regulating genome stability. Chromatin immunoprecipitation; retroviral enforced expression of Id3; Id3 reporter mice; KLRG-1 memory cell analysis Nature immunology High 22057288
2011 Id3hi precursors of long-lived CD8+ memory T cells are identifiable before the peak of T cell expansion using Id3 reporter mice. Deficiency in Id3 results in loss of distinct long-lived memory CD8+ T cell populations. Cytokines differentially regulate Id2 and Id3, linking external cues to gene expression programs controlling memory vs. effector fate. Id3 reporter knock-in mouse; Id3 knockout mouse; flow cytometry of memory populations; cytokine stimulation Nature immunology High 22057289
2011 E2A genome-wide occupancy is altered by pre-TCR-mediated signaling; Id3 expression is higher beyond the pre-TCR checkpoint and remains high in naive T cells. Id3-deficient mice show aberrant effector-memory T cell development, elevated CXCR5 and Bcl-6, and formation of T cell–B cell conjugates and B cell follicles, demonstrating that Id3 antagonizes E2A activity to enforce the naive T cell fate. Id3 knockout mouse; E2A ChIP-seq (genome-wide occupancy); flow cytometry; immunohistology Nature immunology High 21857655
2012 ID1 and ID3 together govern colon cancer-initiating cell (CC-IC) self-renewal through regulation of p21 (CDKN1A). ID1/ID3 regulation of p21 is a central mechanism preventing accumulation of excess DNA damage and functional exhaustion of CC-ICs. Silencing of ID1 and ID3 increases sensitivity to oxaliplatin. siRNA silencing; serial transplantation (CC-IC self-renewal assay); p21 expression analysis; oxaliplatin sensitivity assay Cancer cell Medium 22698403
2012 Burkitt lymphoma carries recurrent somatic mutations in ID3 (68% of cases), concentrated at somatic hypermutation motifs, and many are in regions that could impair ID3 protein function (mapped to focal homozygous loss region at 1p). These mutations are enriched in Burkitt lymphoma compared with other B-cell lymphomas with IG-MYC translocation, establishing ID3 inactivation as a hallmark cooperating event in Burkitt lymphomagenesis. Whole-genome sequencing; whole-exome sequencing; transcriptome sequencing; extended cohort mutation analysis Nature genetics High 23143595
2012 Loss of Id3 in B cells impairs their homing to the aorta and B-cell-mediated atheroprotection; the CCR6 chemokine receptor is identified as an Id3 target mediating aortic B-cell homing. Id3-null B cells transferred into B-cell-deficient mice fail to reconstitute aortic B cells and fail to protect against atherosclerosis. Id3 knockout in Apoe-/- mice; adoptive B-cell transfer; flow cytometry; atherosclerosis quantification; CCR6 expression analysis Circulation research Medium 22034493
2012 ID3 suppresses glioma stem cell invasiveness by inhibiting p27KIP1-RhoA-dependent migration and MMP3 expression; EGFR inhibition decreases ID3 levels, thereby promoting invasion via these downstream effectors. EGFR inhibition; ID3 knockdown; p27KIP1 and MMP3 expression analysis; invasion assay; xenograft and human GBM specimens Cancer letters Medium 23022473
2012 Id3 loss in Ldlr-/- mice increases VCAM-1 expression in vascular smooth muscle cells and aortic tissue. ChIP demonstrates that E12 binds the VCAM-1 promoter in VSMCs, and this binding is inhibited by Id3 overexpression; Id3 deficiency increases macrophage accumulation and accelerates atherosclerosis. Id3 knockout in Ldlr-/- mice; ChIP; VCAM-1 promoter reporter; primary VSMC gain/loss-of-function; immunostaining Arteriosclerosis, thrombosis, and vascular biology Medium 23042815
2014 ID2 and ID3 expression in regulatory T cells is required to suppress fatal inflammatory disease; TCR-driven signaling decreases Id3 abundance to activate a follicular regulatory T (TFR) cell transcription signature, but sustained loss of Id2/Id3 impairs TFR cell development. Id2/Id3 depletion compromises Treg cell maintenance and localization. Conditional Id2/Id3 knockout in Treg cells; flow cytometry; transcriptional profiling; adoptive transfer Nature immunology High 24973820
2015 TGF-β1 and IL-4 downregulate ID3 expression via the kinase TAK1; reduction in ID3 enhances binding of E2A and GATA-3 to the Il9 promoter to promote Il9 transcription and TH9 differentiation. Deletion of Id3 increases IL-9 production from CD4+ T cells, identifying a TAK1–Id3–E2A–GATA-3 pathway governing TH9 fate. Id3 knockout mouse; cytokine stimulation; TAK1 inhibition; chromatin immunoprecipitation (E2A/GATA-3 at Il9 promoter); IL-9 production assay; melanoma model Nature immunology High 26322481
2015 Id3 depletion in adult neural stem/precursor cells (NSPCs) reduces astrocyte generation after cortical brain injury. BMP-2 upregulates Id3 in the SVZ stem cell niche after injury; Id3-deficient NSPCs fail to differentiate into BMP-2-induced astrocytes, while E47-deficient NSPCs differentiate into astrocytes without BMP-2. E47 represses astrocyte-specific gene expression and Id3 antagonizes E47 to promote astrocyte differentiation. Id3 knockout mouse; E47 conditional knockout; cortical injury model; neurosphere culture; astrocyte differentiation assay; BMP-2 treatment The EMBO journal High 26438726
2016 Id3 downregulation in B cells is essential for releasing E2A and E2-2 (redundantly required) for antigen-induced B cell differentiation into germinal center B cells and plasma cells; this pathway controls Blimp1, Xbp1, and CXCR4 expression and is critical for establishing the GC transcriptional network. Id3 knockout mouse; B-cell differentiation assay; flow cytometry; gene expression analysis; antibody titer measurement The Journal of experimental medicine High 27217539
2016 In regulatory T cells, high Id3 expression restricts E47 activity to maintain Foxp3 transcription. Loss of Id3 or overexpression of E47 in Treg cells results in loss of Foxp3 expression; mechanistically, E47 activates Spi-B and SOCS3 expression, both of which downregulate Foxp3. Thus Id3–E47–Spi-B/SOCS3 is the pathway controlling Foxp3 stability. Id3-conditional KO; E47 retroviral overexpression; Foxp3 expression assay in vivo and in vitro; Spi-B and SOCS3 expression analysis Cell reports Medium 27974197
2017 In response to DNA double-strand breaks, ATM phosphorylates ID3 at serine 65 within the HLH motif. This phosphorylation enables a direct interaction between ID3 and MDC1. Depletion of ID3 impairs MDC1 foci formation, suppresses γ-H2AX-bound MDC1, impairs DSB repair, causes cellular hypersensitivity to ionizing radiation, and leads to genomic instability. Disruption of the MDC1–ID3 interaction prevents MDC1 accumulation at DSB sites. Co-immunoprecipitation; ATM kinase assay; phospho-specific mutant analysis; siRNA depletion; immunofluorescence foci assay; comet assay; clonogenic survival assay Nature communications High 29026069
2010 BMP2 stimulates ID3 transcription via BMPR2 and BMPR1A (ALK3) receptors and intracellular SMAD1 and SMAD5 signaling. Two cis-regulatory elements mediate this induction: a novel 6-bp proximal element and a distal SMAD-responsive enhancer. The proximal element does not bind SMADs directly but binds a specific protein complex. Quantitative RT-PCR; promoter-reporter analysis; receptor and SMAD overexpression; RNA interference; cis-element mutagenesis Molecular and cellular endocrinology Medium 21056086
2017 ANGPTL4 binds to cadherin-11, releasing membrane-bound β-catenin, which translocates to the nucleus and transcriptionally upregulates ID3 expression in fibroblasts. ID3 then interacts with scleraxis (a bHLH transcription factor) to inhibit scar-associated collagen types 1α2 and 3α1 production. Co-immunoprecipitation; ANGPTL4/cadherin-11 binding assay; nuclear β-catenin fractionation; Id3 promoter reporter; Id3 siRNA; collagen expression assay Scientific reports Medium 28740178
2018 CD5L promotes M2 macrophage polarization by inducing ID3 expression through an autophagy-dependent pathway requiring ATG7. siRNA targeting ATG7 blocks CD5L-induced ID3 upregulation, and ID3 silencing reverses CD5L-mediated polarization, placing ID3 downstream of CD5L-induced autophagy in macrophage polarization. siRNA silencing of ATG7 and ID3; LC3-II content and colocalization assay; gene expression profiling; flow cytometry Frontiers in immunology Medium 29593730
2019 ID3 interacts with E47 and blocks E47 recruitment to the β-catenin promoter, leading to activation of Wnt/β-catenin signaling and promotion of stemness in intrahepatic cholangiocarcinoma cells. Co-immunoprecipitation (ID3–E47); chromatin immunoprecipitation (E47 at β-catenin promoter); ID3 overexpression/knockdown; Wnt/β-catenin reporter; in vivo xenograft Hepatology Medium 30520117
2024 ID3 is the lineage-determining factor for Kupffer cells that controls the macrophage inhibitory/activating receptor balance and confers anti-tumor phagocytic activity. Mechanistically, ID3 buffers binding of transcription factors ELK1 and E2A at the SIRPA (SIRPα) locus to reduce inhibitory receptor expression. Loss- and gain-of-function in both mouse bone-marrow-derived and human iPSC-derived macrophages confirm ID3 is sufficient to confer potent anti-tumor activity. Id3 loss-of-function and gain-of-function in macrophages; ChIP for ELK1 and E2A at SIRPA locus; phagocytosis assay of live tumor cells; NK/CD8 T cell recruitment assay; human iPSC-derived macrophage experiments Nature High 38326607
2025 ID3 expression identifies a common progenitor of stem-like memory and precursors of exhausted CD8+ T cells (Tpex). ID3 expression itself is required for Tpex cell maintenance during chronic infection and cancer; loss of ID3 results in impaired CD8 T cell immunity. IL-1 family members (IL-36β and IL-18) promote generation of ID3+ stem-like T cells with superior tumor control. Id3 knockout mouse; Id3 reporter; adoptive transfer; chronic infection models; tumor models; cytokine stimulation Science immunology High 39888981

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 757 10537105
2011 The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets. Nature immunology 350 22057289
2012 Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing. Nature genetics 340 23143595
2004 Id2 and Id3 define the potency of cell proliferation and differentiation responses to transforming growth factor beta and bone morphogenetic protein. Molecular and cellular biology 300 15121845
1994 The expression pattern of Id4, a novel dominant negative helix-loop-helix protein, is distinct from Id1, Id2 and Id3. Nucleic acids research 254 8139914
2000 Id2 and Id3 inhibit development of CD34(+) stem cells into predendritic cell (pre-DC)2 but not into pre-DC1. Evidence for a lymphoid origin of pre-DC2. The Journal of experimental medicine 228 11120774
2001 Regulation of the helix-loop-helix proteins, E2A and Id3, by the Ras-ERK MAPK cascade. Nature immunology 221 11175815
2012 ID1 and ID3 regulate the self-renewal capacity of human colon cancer-initiating cells through p21. Cancer cell 187 22698403
2000 Thymocyte selection is regulated by the helix-loop-helix inhibitor protein, Id3. Immunity 173 10661402
2011 Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells. Nature immunology 164 22057288
1996 Expression patterns of Id1, Id2, and Id3 are highly related but distinct from that of Id4 during mouse embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 164 8922523
1999 Impaired immune responses and B-cell proliferation in mice lacking the Id3 gene. Molecular and cellular biology 147 10454544
2001 Id3 inhibits B lymphocyte progenitor growth and survival in response to TGF-beta. Nature immunology 137 11224524
2009 Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent. Immunity 124 19833086
2011 The opposing roles of the transcription factor E2A and its antagonist Id3 that orchestrate and enforce the naive fate of T cells. Nature immunology 119 21857655
2014 Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease. Nature immunology 118 24973820
2004 A T cell intrinsic role of Id3 in a mouse model for primary Sjogren's syndrome. Immunity 107 15485632
2018 CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3. Frontiers in immunology 104 29593730
2011 B-cell aortic homing and atheroprotection depend on Id3. Circulation research 100 22034493
1997 Regulation of Id3 cell cycle function by Cdk-2-dependent phosphorylation. Molecular and cellular biology 93 9372912
2007 Id1, but not Id3, directs long-term repopulating hematopoietic stem-cell maintenance. Blood 85 17622570
2009 Id3 is a direct transcriptional target of Pax7 in quiescent satellite cells. Molecular biology of the cell 82 19458195
2002 Redox-sensitive vascular smooth muscle cell proliferation is mediated by GKLF and Id3 in vitro and in vivo. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 81 12087069
1999 Disruption of alpha beta but not of gamma delta T cell development by overexpression of the helix-loop-helix protein Id3 in committed T cell progenitors. The EMBO journal 81 10329625
2015 The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells. Nature immunology 77 26322481
2004 Induction of Id1 and Id3 by latent membrane protein 1 of Epstein-Barr virus and regulation of p27/Kip and cyclin-dependent kinase 2 in rodent fibroblast transformation. Journal of virology 74 15564458
2009 Id3 restricts the developmental potential of gamma delta lineage during thymopoiesis. Journal of immunology (Baltimore, Md. : 1950) 70 19380777
2009 Ebf1-mediated down-regulation of Id2 and Id3 is essential for specification of the B cell lineage. Proceedings of the National Academy of Sciences of the United States of America 69 19122139
1997 Id3 prevents differentiation of preadipose cells. Molecular and cellular biology 69 9121427
2002 Identification of a novel redox-sensitive gene, Id3, which mediates angiotensin II-induced cell growth. Circulation 67 12021231
2024 The nuclear factor ID3 endows macrophages with a potent anti-tumour activity. Nature 66 38326607
2005 Adenoviral gene transfer of BMP-7, Id2, or Id3 suppresses injury-induced epithelial-to-mesenchymal transition of lens epithelium in mice. American journal of physiology. Cell physiology 66 16120655
2010 Targeting Id1 and Id3 by a specific peptide aptamer induces E-box promoter activity, cell cycle arrest, and apoptosis in breast cancer cells. Breast cancer research and treatment 60 20191379
2008 The helix-loop-helix factors Id3 and E47 are novel regulators of adiponectin. Circulation research 60 18669923
1996 E2A basic-helix-loop-helix transcription factors are negatively regulated by serum growth factors and by the Id3 protein. Nucleic acids research 58 8759016
2016 Dynamic changes in Id3 and E-protein activity orchestrate germinal center and plasma cell development. The Journal of experimental medicine 57 27217539
2004 Inhibitory helix-loop-helix transcription factors Id1/Id3 promote bone formation in vivo. Journal of cellular biochemistry 55 15368360
2015 The balance of Id3 and E47 determines neural stem/precursor cell differentiation into astrocytes. The EMBO journal 54 26438726
1996 Muscle cell differentiation is inhibited by the helix-loop-helix protein Id3. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 54 8853903
2015 Inflammation-induced S100A8 activates Id3 and promotes colorectal tumorigenesis. International journal of cancer 52 26135667
2005 Targeting Id1 and Id3 inhibits peritoneal metastasis of gastric cancer. Cancer science 51 16271072
1996 Regulation of cell differentiation in C2C12 myoblasts by the Id3 helix-loop-helix protein. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 51 8853902
2004 Ubiquitin-dependent degradation of Id1 and Id3 is mediated by the COP9 signalosome. Journal of molecular biology 48 15451666
2016 ITF2357 transactivates Id3 and regulate TGFβ/BMP7 signaling pathways to attenuate corneal fibrosis. Scientific reports 45 26865052
2012 Id1 and Id3 expression is associated with increasing grade of prostate cancer: Id3 preferentially regulates CDKN1B. Cancer medicine 45 23342268
2004 Intron retention generates a novel Id3 isoform that inhibits vascular lesion formation. The Journal of biological chemistry 44 15159391
2012 BMP9 induces EphrinB2 expression in endothelial cells through an Alk1-BMPRII/ActRII-ID1/ID3-dependent pathway: implications for hereditary hemorrhagic telangiectasia type II. Angiogenesis 43 22622516
2011 ID1 and ID3 represent conserved negative regulators of human embryonic and induced pluripotent stem cell hematopoiesis. Journal of cell science 43 21486943
2017 Relevance of ID3-TCF3-CCND3 pathway mutations in pediatric aggressive B-cell lymphoma treated according to the non-Hodgkin Lymphoma Berlin-Frankfurt-Münster protocols. Haematologica 42 28209658
1995 Expression of the helix-loop-helix gene Id3 during murine embryonic development. Developmental dynamics : an official publication of the American Association of Anatomists 41 7655079
2013 Id1 and Id3 co-expression correlates with clinical outcome in stage III-N2 non-small cell lung cancer patients treated with definitive chemoradiotherapy. Journal of translational medicine 40 23311395
2018 Cutting Edge: Dynamic Expression of Id3 Defines the Stepwise Differentiation of Tissue-Resident Regulatory T Cells. Journal of immunology (Baltimore, Md. : 1950) 37 30518568
2011 Modeling Sjögren's syndrome with Id3 conditional knockout mice. Immunology letters 37 20932862
2019 ID3 Promotes Stem Cell Features and Predicts Chemotherapeutic Response of Intrahepatic Cholangiocarcinoma. Hepatology (Baltimore, Md.) 36 30520117
2001 Vascular injury induces posttranscriptional regulation of the Id3 gene: cloning of a novel Id3 isoform expressed during vascular lesion formation in rat and human atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 34 11348870
1998 Lymphoid-specific expression of the Id3 gene in hematopoietic cells. Selective antagonism of E2A basic helix-loop-helix protein associated with Id3-induced differentiation of erythroleukemia cells. The Journal of biological chemistry 33 9525934
2021 Heme Oxygenase-1 (HMOX-1) and inhibitor of differentiation proteins (ID1, ID3) are key response mechanisms against iron-overload in pancreatic β-cells. Molecular and cellular endocrinology 32 34547407
2013 Small molecule antagonist of the bone morphogenetic protein type I receptors suppresses growth and expression of Id1 and Id3 in lung cancer cells expressing Oct4 or nestin. Molecular cancer 31 24160469
2012 Blockade of EGFR signaling promotes glioma stem-like cell invasiveness by abolishing ID3-mediated inhibition of p27(KIP1) and MMP3 expression. Cancer letters 31 23022473
2012 Inhibitor of differentiation 1 (Id1) and Id3 proteins play different roles in TGFβ effects on cell proliferation and migration in prostate cancer cells. The Prostate 31 23060149
2001 Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas. British journal of cancer 31 11161400
2001 Glucose and other insulin secretagogues induce, rather than inhibit, expression of Id-1 and Id-3 in pancreatic islet beta cells. Diabetologia 31 11357476
2021 EGF stimulates human trophoblast cell invasion by downregulating ID3-mediated KISS1 expression. Cell communication and signaling : CCS 29 34620174
2016 Id3 Maintains Foxp3 Expression in Regulatory T Cells by Controlling a Transcriptional Network of E47, Spi-B, and SOCS3. Cell reports 29 27974197
2010 Mutation of inhibitory helix-loop-helix protein Id3 causes γδ T-cell lymphoma in mice. Blood 29 20852128
2007 Id3 is a novel regulator of p27kip1 mRNA in early G1 phase and is required for cell-cycle progression. Oncogene 29 17404577
2014 Increased expression of Id1 and Id3 promotes tumorigenicity by enhancing angiogenesis and suppressing apoptosis in small cell lung cancer. Genes & cancer 28 25061504
2013 Id3 and Id2 act as a dual safety mechanism in regulating the development and population size of innate-like γδ T cells. Journal of immunology (Baltimore, Md. : 1950) 28 24379125
2013 Id2, Id3 and Id4 overcome a Smad7-mediated block in tumorigenesis, generating TGF-β-independent melanoma. Carcinogenesis 27 24343358
2017 Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma. Journal of neuro-oncology 26 28283800
2010 Mechanisms of bone morphogenetic protein 2 (BMP2) stimulated inhibitor of DNA binding 3 (Id3) transcription. Molecular and cellular endocrinology 26 21056086
2017 ID3 regulates the MDC1-mediated DNA damage response in order to maintain genome stability. Nature communications 25 29026069
2017 New role of ID3 in melanoma adaptive drug-resistance. Oncotarget 25 29299138
2016 Id3 Orchestrates Germinal Center B Cell Development. Molecular and cellular biology 25 27457619
2013 Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion. Journal of immunology (Baltimore, Md. : 1950) 25 24123680
2011 The Id3/E47 axis mediates cell-cycle control in human pancreatic ducts and adenocarcinoma. Molecular cancer research : MCR 25 21498546
2010 Developmental ablation of Id1 and Id3 genes in the vasculature leads to postnatal cardiac phenotypes. Developmental biology 25 20937270
1995 Expression of Id2 and Id3 mRNA in human lymphocytes. Leukemia research 25 8632670
2017 Regulatory Axis of miR-195/497 and HMGA1-Id3 Governs Muscle Cell Proliferation and Differentiation. International journal of biological sciences 24 28255268
2011 Id3 upregulates BrdU incorporation associated with a DNA damage response, not replication, in human pancreatic β-cells. Islets 24 21964314
2025 Stem-like memory and precursors of exhausted T cells share a common progenitor defined by ID3 expression. Science immunology 23 39888981
2021 ID1/ID3 mediate the contribution of skin fibroblasts to local nerve regeneration through Itga6 in wound repair. Stem cells translational medicine 23 34520124
2020 Id1 and Id3 Maintain Steady-State Hematopoiesis by Promoting Sinusoidal Endothelial Cell Survival and Regeneration. Cell reports 23 32348770
2021 Prosurvival IL-7-Stimulated Weak Strength of mTORC1-S6K Controls T Cell Memory via Transcriptional FOXO1-TCF1-Id3 and Metabolic AMPKα1-ULK1-ATG7 Pathways. Journal of immunology (Baltimore, Md. : 1950) 22 34872976
2017 Angiopoietin-like 4 induces a β-catenin-mediated upregulation of ID3 in fibroblasts to reduce scar collagen expression. Scientific reports 22 28740178
2013 ID3 mutations are recurrent events in double-hit B-cell lymphomas. Anticancer research 22 24222112
2006 Id3 induces a caspase-3- and -9-dependent apoptosis and mediates UVB sensitization of HPV16 E6/7 immortalized human keratinocytes. Oncogene 21 16449966
2005 Id3 induces growth arrest and caspase-2-dependent apoptosis in B lymphocyte progenitors. Journal of immunology (Baltimore, Md. : 1950) 21 16177095
2021 Bone Morphogenetic Protein 4 Alleviates DSS-Induced Ulcerative Colitis Through Activating Intestinal Stem Cell by Target ID3. Frontiers in cell and developmental biology 20 34692671
2020 miR-212-5p exerts tumor promoter function by regulating the Id3/PI3K/Akt axis in lung adenocarcinoma cells. Journal of cellular physiology 20 32039486
2012 Loss of Id3 increases VCAM-1 expression, macrophage accumulation, and atherogenesis in Ldlr-/- mice. Arteriosclerosis, thrombosis, and vascular biology 20 23042815
2022 Id3 expression identifies CD4+ memory Th1 cells. Proceedings of the National Academy of Sciences of the United States of America 19 35858332
2015 ID3 contributes to the acquisition of molecular stem cell-like signature in microvascular endothelial cells: its implication for understanding microvascular diseases. Microvascular research 19 25665868
2004 E2A/HEB and Id3 proteins control the sensitivity to glucocorticoid-induced apoptosis in thymocytes by regulating the SRG3 expression. The Journal of biological chemistry 19 15016815
2022 Corneal fibrosis abrogation by a localized AAV-mediated inhibitor of differentiation 3 (Id3) gene therapy in rabbit eyes in vivo. Molecular therapy : the journal of the American Society of Gene Therapy 18 35780298
2021 Circ-SKA3 upregulates ID3 expression by decoying miR-326 to accelerate the development of medulloblastoma. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 18 33775353
2017 Aberrant expressions of endometrial Id3 and CTLA-4 are associated with unexplained repeated implantation failure and recurrent miscarriage. American journal of reproductive immunology (New York, N.Y. : 1989) 18 28224680
2012 Wnt/β-catenin signaling changes C2C12 myoblast proliferation and differentiation by inducing Id3 expression. Biochemical and biophysical research communications 18 22326917
2012 FHL2 inhibits the Id3-promoted proliferation and invasive growth of human MCF-7 breast cancer cells. Chinese medical journal 18 22882857
2002 Expression of the helix-loop-helix gene id3 in the zebrafish embryo. Mechanisms of development 17 11900982

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