Affinage

ID4

DNA-binding protein inhibitor ID-4 · UniProt P47928

Length
161 aa
Mass
16.6 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ID4 is a helix-loop-helix (HLH) protein that lacks the DNA-binding basic region and acts as a dominant-negative regulator of differentiation timing, proliferation, and stem cell state across multiple lineages (PMID:8139914, PMID:15469968). Its core biochemical activity is sequestration: through its HLH domain it heterodimerizes with bHLH transcription factors (E47, MyoD, Neurogenin, NeuroD, Twist1, HEB) to block their DNA binding and trans-activation (PMID:8139914, PMID:7665172, PMID:14651922, PMID:24413082, PMID:33554073), and it also dimerizes with other ID proteins (ID1-3), acting as an "inhibitor of inhibitors" that can paradoxically free E47 by titrating ID1 (PMID:25778840). This sequestration logic underlies its developmental roles: ID4 sustains progenitor proliferation and prevents premature differentiation in cortical neural progenitors, oligodendrocyte precursors, mammary stem cells, and spermatogonial stem cells, with loss causing precocious differentiation in each (PMID:15469968, PMID:16862533, PMID:15882580, PMID:25813983, PMID:28087628). In adult hippocampal neural stem cells ID4 enforces quiescence downstream of Notch2, in part by sequestering E47 to promote degradation of the pro-activation bHLH factor Ascl1 (PMID:31390563, PMID:31552825). ID4 directs lineage choice through specific partners: it antagonizes HEB to prevent myoepithelial differentiation in mammary cells (PMID:33554073), releases Hes1 from Hes1-Hey2 complexes to stabilize Runx2 and promote osteoblast over adipocyte fate (PMID:20628571), and is required for adipocyte differentiation via C/EBPalpha and PPARgamma (PMID:20460371). ID4 is itself tightly regulated transcriptionally — by USF1/Sp1-Sp3 promoter elements, cAMP/PKA signaling, MeCP2 repression, and a mutant p53-E2F1 complex — and is epigenetically silenced in cancers by EZH2/H3K27me3-initiated, DNMT-dependent promoter methylation (PMID:9516472, PMID:10066362, PMID:16682435, PMID:19783986, PMID:25115397, PMID:34482420). Beyond transcription factor sequestration, ID4 has acquired direct protein- and RNA-level functions in cancer: it forms a complex with CBP/p300 and p53 to drive p53 acetylation at K373 and restore p53 transcriptional activity (PMID:24330748, PMID:27911860), binds and stabilizes pro-angiogenic IL8 and GRO-alpha mRNAs downstream of mutant p53 (PMID:19783986), recruits the lncRNA MALAT1 via SRSF1 to reshape VEGFA splicing (PMID:28652379), and interacts with FKBP52 to restrain androgen receptor signaling, with ID4 loss promoting castration-resistant prostate cancer (PMID:24921661, PMID:28252832). ID4 is also a negative transcriptional regulator of the ERalpha axis (Esr1, FoxA1) and BRCA1, and associates with MDC1 at damaged chromatin, implicating it in the DNA damage response (PMID:11136250, PMID:25038044, PMID:32527287).

Mechanistic history

Synthesis pass · year-by-year structured walk · 34 steps
  1. 1994 High

    Established ID4's foundational biochemical identity: a basic-region-less HLH protein that inhibits bHLH factors, defining its mechanism of action.

    Evidence In vitro EMSA with recombinant ID4 against E47 homodimers and E47/MyoD heterodimers

    PMID:8139914

    Open questions at the time
    • In vitro binding does not establish which bHLH partners are physiologically relevant in vivo
    • No cellular phenotype demonstrated
  2. 1995 Medium

    Confirmed the dominant-negative activity in cells, showing ID4 represses MyoD-driven transcription at an E-box enhancer.

    Evidence MCK-luciferase reporter assay in transfected mammalian cells

    PMID:7665172

    Open questions at the time
    • Single reporter system
    • Endogenous muscle differentiation not tested
  3. 1998 High

    Mapped the cis-regulatory architecture controlling ID4's own transcription, revealing USF1 activation and Sp1/Sp3 repression plus autoregulatory feedback.

    Evidence EMSA and reporter assays including heterologous Drosophila SL2 cells

    PMID:9516472

    Open questions at the time
    • Promoter context studied in transfection, not endogenous chromatin
    • Physiological signals driving USF1/Sp1 occupancy not defined
  4. 1999 Medium

    Linked ID4 expression to cAMP signaling and revealed a pro-apoptotic consequence of overexpression in astrocytes.

    Evidence Pharmacological cAMP modulation of primary astrocytes and overexpression with apoptosis readout

    PMID:10066362

    Open questions at the time
    • Mechanism connecting cAMP to Id4 promoter not resolved
    • Apoptosis phenotype may be overexpression artifact
  5. 2000 High

    Defined ID4 as a differentiation-timing switch in oligodendrocyte precursors, where its downregulation permits differentiation.

    Evidence Retroviral overexpression in OPCs with mitogen-withdrawal and thyroid hormone differentiation assays

    PMID:10790366

    Open questions at the time
    • bHLH partners mediating the block not identified
    • Loss-of-function not yet tested
  6. 2001 Medium

    Distinguished ID4 from other ID family members through isoform-specific hormonal regulation (FSH/cAMP-induced) and dispensability for transferrin promoter activation.

    Evidence RT-PCR, Northern blot, antisense oligonucleotide plus reporter assay in Sertoli cells

    PMID:11316735

    Open questions at the time
    • Functional role of FSH-induced Id4 in Sertoli cells unclear
    • No direct target identified
  7. 2001 Medium

    Identified ID4 as a negative regulator of the BRCA1 promoter and linked it to anchorage-independent growth.

    Evidence Ribozyme library screen with BRCA1-promoter EGFP reporter and expression modulation in ovarian cancer cells

    PMID:11136250

    Open questions at the time
    • Mechanism of BRCA1 promoter repression not defined
    • Direct vs indirect regulation unresolved
  8. 2003 Medium

    Revealed epigenetic silencing of ID4 by promoter hypermethylation in gastric cancer, establishing ID4 as a methylation-regulated locus.

    Evidence Bisulfite sequencing, MSP, and pharmacological demethylation with RT-PCR

    PMID:14534543

    Open questions at the time
    • Causality of silencing for tumor phenotype not tested
    • Enzymes initiating methylation not identified
  9. 2003 Medium

    Extended ID4's proliferation/differentiation switch and oncogenic potential to mammary epithelium.

    Evidence Stable/transient Id4 transfection in HC11 cells with proliferation, beta-casein reporter, and soft agar assays

    PMID:14633621

    Open questions at the time
    • bHLH targets in mammary cells not identified
    • In vivo relevance not addressed
  10. 2003 Medium

    Demonstrated differential bHLH substrate specificity among ID proteins, with ID4 uniquely inhibiting neurogenin, neuroD, and MyoD.

    Evidence Xenopus animal cap and in vivo overexpression assays comparing Id2/3/4

    PMID:14651922

    Open questions at the time
    • Structural basis of specificity not defined
    • Ortholog data may not fully translate to mammalian ID4
  11. 2004 High

    Provided genetic proof that ID4 controls neural progenitor G1-S transition and prevents premature neuronal differentiation in vivo.

    Evidence Id4-knockout mice with BrdU, IHC, and neurosphere assays

    PMID:15469968

    Open questions at the time
    • Molecular bHLH targets in cortical progenitors not pinpointed
    • Cell-cycle machinery link not detailed
  12. 2005 High

    Genetically confirmed ID4 as a brake on oligodendrocyte and astrocyte differentiation, controlling neocortical neuron output and glial timing.

    Evidence Id4-knockout mice plus retroviral overexpression with myelin-gene reporters and BMP2 differentiation assays

    PMID:15882580 PMID:16862533

    Open questions at the time
    • Direct transcriptional effectors of myelin gene regulation not resolved
    • Interplay with BMP signaling mechanistically incomplete
  13. 2006 Medium

    Placed ID4 within MeCP2-dependent neuronal gene regulation, with ID4 derepressed in Mecp2-deficient brain.

    Evidence ChIP, qRT-PCR, and immunofluorescence in Mecp2-deficient mouse and Rett syndrome brain

    PMID:16682435

    Open questions at the time
    • Direct MeCP2 binding shown for ID1-3 but ID4 inferred from expression change
    • Functional consequence of ID4 derepression not tested
  14. 2009 High

    Connected ID4 to oncogenic gain-of-function p53, showing a mutant p53-E2F1 complex drives ID4 transcription and ID4 then stabilizes pro-angiogenic IL8/GRO-alpha mRNAs.

    Evidence ChIP on ID4 promoter, RIP and mRNA stability assays, mutant p53 knockdown, angiogenesis assays

    PMID:19783986

    Open questions at the time
    • RNA-binding domain/mode of ID4 not structurally defined
    • Generality across mutant p53 alleles addressed only later
  15. 2009 Medium

    Implicated ID4 in prostate cancer cell cycle/apoptosis control and linked its loss to AR pathway changes, with promoter hypermethylation in DU145.

    Evidence Ectopic expression in DU145 with cell cycle, apoptosis, marker expression, and MSP

    PMID:19500415

    Open questions at the time
    • Mechanism linking ID4 to AR/p21/p27/p53 not yet defined here
    • Correlative marker changes only
  16. 2010 High

    Defined ID4 as a determinant of mesenchymal lineage choice — required for adipogenesis and, via an Id4-Hes1-Hey2-Runx2 axis, for osteoblast over adipocyte fate.

    Evidence Id4-knockout mice, ST2 knockdown, expression profiling, Co-IP for Hes1-Hey2, Runx2 activity assays

    PMID:20460371 PMID:20628571

    Open questions at the time
    • Direct ID4-Hes1 binding vs displacement mechanism not fully resolved
    • Reconciliation of pro-adipogenic and anti-adipogenic roles across tissues incomplete
  17. 2011 High

    Revealed non-canonical ID4 functions: a miR-9*/SOX2/ABC-transporter axis driving glioma chemoresistance and p38MAPK suppression controlling mammary ductal expansion.

    Evidence shRNA/miRNA modulation with 3'-UTR reporters and drug assays; Id4-KO/siRNA with p38MAPK phosphorylation and inhibitor rescue

    PMID:21531766 PMID:22069192

    Open questions at the time
    • How ID4 suppresses miR-9* or p38MAPK mechanistically not defined
    • Direct vs indirect effects unresolved
  18. 2013 Medium

    Identified direct ID4-Twist1 interaction as a brake on glioblastoma invasiveness through MMP2 repression.

    Evidence Co-IP, MMP2 reporter, invasion assay, siRNA, and TCGA correlation

    PMID:24413082

    Open questions at the time
    • Single Co-IP without reciprocal/structural validation of the interaction
    • In vivo invasion not tested
  19. 2013 High

    Established a protein-level ID4 function distinct from bHLH sequestration: ID4-CBP/p300-p53 complex formation drives p53 K373 acetylation to restore p53 DNA binding and transcriptional/apoptotic activity.

    Evidence Co-IP of ID4-p53-CBP/p300, acetylation Western, EMSA, reporter, and apoptosis assays

    PMID:24330748

    Open questions at the time
    • Whether ID4 directly contacts p300 or p53 to position acetylation not dissected
    • Structural basis unknown
  20. 2017 High

    Pinpointed K373 as the critical ID4-dependent p53 acetylation site using acetylation-mimic mutants, solidifying the ID4-p53 activation mechanism.

    Evidence K373Q/K373R p53 mutants with DNA-binding, target expression, and cell cycle/apoptosis assays in p53-null cells

    PMID:27911860

    Open questions at the time
    • Mechanism by which ID4 enhances CBP/p300 catalysis not resolved
    • In vivo relevance of K373 axis not tested
  21. 2014 High

    Defined ID4 as a downstream effector and quiescence factor of Notch2 in adult hippocampal neural stem cells, with loss activating NSC proliferation.

    Evidence Conditional Id4 knockout, shRNA, Notch2 gain-of-function, BrdU and neurosphere assays

    PMID:31390563

    Open questions at the time
    • Direct Notch2-to-Id4 transcriptional link not mapped here
    • Effector bHLH targets defined only in later work
  22. 2014 High

    Established ID4's role in mammary stem cell biology as a negative regulator of the ERalpha signaling axis through direct promoter binding.

    Evidence Conditional Id4 knockout mice with ChIP on Esr1/Foxa1 promoters and target expression analysis

    PMID:25038044

    Open questions at the time
    • How a basic-region-less protein binds these promoters (direct vs co-factor) not resolved
    • bHLH partner mediating repression not identified here
  23. 2014 High

    Defined the epigenetic silencing mechanism of ID4 in cancer: EZH2/H3K27me3 initiates and DNMT1 maintains promoter methylation.

    Evidence ChIP for EZH2/H3K27me3/DNMT1 on ID4 promoter and EZH2 knockdown reactivation in prostate cancer cells

    PMID:25115397

    Open questions at the time
    • Upstream signals recruiting EZH2 to ID4 not defined
    • Tissue generality of this mechanism beyond prostate not established here
  24. 2014 High

    Refined the inter-ID interaction logic, showing ID4 dimerizes with ID1-3 and can free E47 by sequestering ID1, acting as an inhibitor of inhibitors.

    Evidence Co-IP, EMSA competition for E47 binding, immunofluorescence colocalization, and domain-deletion mutagenesis

    PMID:25778840

    Open questions at the time
    • Physiological contexts where the inhibitor-of-inhibitors mode dominates not defined
    • Quantitative dimer preferences not measured
  25. 2014 High

    Connected ID4 loss to castration-resistant prostate cancer through constitutive AR activation and de novo steroidogenesis.

    Evidence Stable shRNA silencing in LNCaP, RNA-seq, and castration xenograft model

    PMID:24921661

    Open questions at the time
    • Molecular link from ID4 to AR activation defined in subsequent FKBP52 work
    • Steroidogenic enzyme regulation mechanism incomplete
  26. 2015 High

    Identified ID4 as a marker and driver of mammary stem cell self-renewal that suppresses luminal differentiation factors.

    Evidence ID4-GFP knock-in reporter mouse, single-cell transcriptomics, FACS, and mammary reconstitution

    PMID:25813983

    Open questions at the time
    • bHLH effectors of the self-renewal program defined only in later HEB work
    • Direct target genes from this study limited
  27. 2016 High

    Provided the molecular basis for ID4-mediated AR restraint: direct ID4-FKBP52 interaction (not direct AR binding) that limits FKBP52-dependent AR activity.

    Evidence Proteomics, in vitro binding/Co-IP, AR reporter, and MJC13 pharmacological rescue in xenografts

    PMID:28252832

    Open questions at the time
    • Structural mode of ID4-FKBP52 binding not resolved
    • Whether HLH domain mediates this interaction not established
  28. 2017 High

    Extended ID4's RNA-level oncogenic functions, showing ID4 with mutant p53 recruits MALAT1 via SRSF1 to chromatin to reshape VEGFA splicing.

    Evidence RIP, Co-IP, RNA-FISH for MALAT1 localization, and VEGFA isoform analysis with shRNA

    PMID:28652379

    Open questions at the time
    • Direct vs SRSF1-bridged ID4-MALAT1 association not dissected
    • Functional output of altered VEGFA isoforms only partly characterized
  29. 2017 High

    Established ID4 as a dosage-sensitive determinant of spermatogonial stem cell vs progenitor identity, with high ID4 maintaining the stem state.

    Evidence Id4-eGFP reporter and conditional overexpression mice, RNA-seq, FACS, and transplantation

    PMID:28087628

    Open questions at the time
    • bHLH partners enforcing SSC state not identified
    • Transcriptional targets in SSCs not mapped
  30. 2019 High

    Resolved a mechanism for ID4-enforced NSC quiescence: ID4 sequesters E47 to drive degradation of the pro-activation factor Ascl1.

    Evidence Conditional Id4 knockout, overexpression in NSCs, Ascl1 protein analysis, and E47-Ascl1-Id4 Co-IP

    PMID:31552825

    Open questions at the time
    • Degradation machinery acting on freed Ascl1 not identified
    • Generalizability to other quiescent niches untested
  31. 2020 High

    Revealed a transcription-independent chromatin role for ID4 in the DNA damage response via MDC1, gammaH2AX, and BRCA1 at fragile sites.

    Evidence RIME endogenous interactome, ChIP-seq, RNA-seq, and immunoprecipitation in breast cancer cells

    PMID:32527287

    Open questions at the time
    • Functional consequence of ID4 at damage sites for repair efficiency not established
    • Whether ID4 recruits or stabilizes MDC1 unclear
  32. 2021 High

    Identified HEB as the key bHLH partner through which ID4 blocks mammary myoepithelial differentiation, linking sequestration to lineage gene control.

    Evidence Mass spectrometry interactome, HEB ChIP-seq, conditional Id4 knockout organoids/mice, and RNA-seq

    PMID:33554073

    Open questions at the time
    • Stoichiometry of ID4-HEB control at individual loci not quantified
    • Interplay with the ERalpha-suppressing role not integrated
  33. 2021 High

    Provided causal epigenetic proof that DNA methylation of the Id4 promoter is sufficient to drive OPC differentiation.

    Evidence CRISPR/dCas9-DNMT3a targeted methylation of the Id4 promoter with OPC differentiation readout

    PMID:34482420

    Open questions at the time
    • Endogenous signals triggering this methylation in vivo not defined
    • Contribution of co-targeted Id2 not fully separated
  34. 2024 Medium

    Described a paracrine ID4 oncogenic circuit: ID4-driven VEGFA secretion activates VEGFR2-integrin beta3-focal adhesion signaling and YAP/TAZ in breast cancer.

    Evidence ID4 overexpression/knockdown, conditioned-media paracrine assays, VEGFR2-integrin beta3 Co-IP, VEGFA ELISA, YAP/TAZ localization, invasion assays

    PMID:38321003

    Open questions at the time
    • How ID4 transcriptionally/post-transcriptionally raises VEGFA secretion not pinned down
    • In vivo significance of the YAP/TAZ axis not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a protein lacking a DNA-binding basic region achieves direct promoter occupancy (e.g., on Esr1/Foxa1/ID4-target genes) and integrates its many partner-specific functions—bHLH sequestration, p53 acetylation, RNA stabilization/splicing, FKBP52-AR restraint, and DNA-damage chromatin association—into context-dependent outputs remains unresolved.
  • No structural model of ID4 in any of its protein/RNA complexes
  • Mechanism of ID4 chromatin recruitment without a basic domain unknown
  • Rules governing which partner dominates in a given cell type undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0003723 RNA binding 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 2
Pathway
R-HSA-1266738 Developmental Biology 8 R-HSA-1643685 Disease 5 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 2 R-HSA-73894 DNA Repair 1
Partners
E47FKBP52HEBID1MDC1MYODSRSF1TWIST1
Complex memberships
ID4-CBP/p300-p53 complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 ID4 protein contains an HLH dimerization domain but lacks the DNA-binding basic region, functioning as a dominant-negative inhibitor of bHLH transcription factors; ID4 inhibits DNA-binding of E47 homodimers and E47/MyoD heterodimers in vitro. In vitro DNA-binding assay (gel shift/EMSA) with recombinant proteins Nucleic acids research High 8139914
1995 Enforced expression of ID4 (Id-4H) inhibits trans-activation of the muscle creatine kinase E-box enhancer by MyoD in transfection experiments, confirming dominant-negative function. Transient transfection reporter assay (E-box/MCK enhancer-luciferase) in mammalian cells Genomics Medium 7665172
1998 The human ID4 promoter is regulated by two functional elements: (1) an E-box bound by the bHLH-zip protein USF1 that stimulates transcription (enforced USF1 increases E-box-mediated promoter activity), and ID4 itself blocks this stimulation via heterodimerization with bHLH factors; (2) a downstream GA motif recognized by Sp1 and Sp3 that represses ID4 transcription ~20-fold. Transient transfection reporter assay, gel mobility shift assay (EMSA), transfection into Drosophila SL2 cells The Journal of biological chemistry High 9516472
1999 The cAMP-dependent signaling pathway (activated by dibutyryl-cAMP, forskolin, or pentoxifylline) selectively and dramatically decreases Id4 gene expression in primary astrocytes; overexpression of Id4 in an astrocyte-derived cell line induces apoptosis (cells round up and die). Pharmacological treatment of primary astrocyte cultures, Northern blot, overexpression by transfection with morphological/apoptosis readout Experimental cell research Medium 10066362
2000 Enforced expression of Id4 in oligodendrocyte precursor cells (OPCs) stimulates proliferation and blocks differentiation induced by mitogen withdrawal or thyroid hormone; Id4 mRNA and protein decrease together under pro-differentiation conditions, indicating transcriptional control as part of a differentiation-timing mechanism. Retroviral overexpression in OPC cultures, differentiation induction by mitogen withdrawal and thyroid hormone treatment, Northern and Western blot for Id4 The EMBO journal High 10790366
2001 Id4 expression in Sertoli cells is induced by FSH or cAMP (mimicking FSH via PKA pathway), whereas Id1 is downregulated by FSH; antisense to Id4 had no effect on FSH-mediated transferrin promoter activation in Sertoli cells, unlike Id1 and Id2. Immunoprecipitation with isoform-specific antibodies, RT-PCR, Northern blot, antisense oligonucleotide transfection with transferrin promoter reporter assay Endocrinology Medium 11316735
2001 Ribozyme-mediated knockdown of ID4 upregulates BRCA1 expression in human ovarian cancer cells (identified by inverse genomics), and increased ID4 expression correlates with anchorage-independent growth; ID4 acts as a negative regulator of BRCA1 promoter activity. Randomized ribozyme gene library screen with EGFP reporter under BRCA1 promoter, target gene identification and modulation experiments Proceedings of the National Academy of Sciences of the United States of America Medium 11136250
2003 ID4 promoter hypermethylation silences ID4 expression in gastric cancer; treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (with or without trichostatin A) restores ID4 expression and is accompanied by promoter demethylation. ID4 promoter methylation significantly associates with hMLH1 methylation and microsatellite instability. Bisulfite genomic sequencing, methylation-specific PCR, RT-PCR, pharmacological demethylation Oncogene Medium 14534543
2003 Id4 overexpression in HC11 mammary epithelial cells increases cell proliferation, inhibits lactogenic hormone-mediated differentiation (reduces beta-casein promoter activity and expression), and induces anchorage-independent growth in soft agar. Transient and stable transfection of Id4, proliferation assay, beta-casein promoter reporter assay, soft agar colony assay The American journal of pathology Medium 14633621
2003 Xenopus Id4 can inhibit the neurogenic activity of neurogenin and neuroD and the myogenic activity of MyoD in animal cap and in vivo overexpression assays, whereas Id2 inhibits only MyoD and neuroD, and Id3 blocks only neuroD—demonstrating differential substrate specificity among Id proteins. Animal cap explant assay, in vivo overexpression in Xenopus embryos, reporter assay Developmental biology Medium 14651922
2004 Id4 is required for normal G1-S transition in early cortical progenitors; Id4-null mice show reduced proliferation of ventricular zone stem cells and premature neuronal differentiation, demonstrating that Id4 regulates neural progenitor proliferation and differentiation in vivo. Id4-knockout mouse analysis, BrdU incorporation, immunohistochemistry, in vitro neurosphere cultures Development (Cambridge, England) High 15469968
2005 Id4 deficiency in mice leads to precocious oligodendrocyte differentiation both in vitro and in vivo; overexpression of Id4 in OPC progenitors prevents differentiation and decreases myelin gene expression (MBP, CGT but not PLP promoters), and Id4 differentially regulates myelin protein expression and subcellular distribution. Id4-knockout mouse analysis, overexpression via retroviral transduction, luciferase reporter assay for CGT/MBP/PLP promoters, immunohistochemistry Glia High 16862533
2005 Id4 deficiency causes premature neuronal differentiation resulting in a thicker neocortex with more early-born neurons; adult Id4-/- brains are smaller with depleted late-born cortical neurons and astrocytes, and neurosphere proliferation is impaired; BMP2-mediated astrocyte differentiation is accelerated in Id4-/- NPCs. Id4-knockout mouse analysis, immunohistochemistry, neurosphere culture, BMP2 treatment assay Developmental biology High 15882580
2006 All four ID genes (ID1-4) are neuronal targets repressed by MeCP2; chromatin immunoprecipitation confirmed MeCP2 binding near/within ID1, ID2, ID3 promoters; ID4 mRNA and protein are increased in Mecp2-deficient mouse brain. Chromatin immunoprecipitation (ChIP), quantitative RT-PCR, immunofluorescence, laser scanning cytometry in Mecp2-deficient mouse and human RTT brain Human molecular genetics Medium 16682435
2009 The protein complex mutant p53-E2F1 assembles on specific regions of the ID4 promoter and positively controls ID4 transcription; ID4 protein then binds to and stabilizes mRNAs encoding pro-angiogenic factors IL8 and GRO-alpha, increasing angiogenic potential in mutant p53-expressing cancer cells. Chromatin immunoprecipitation (ChIP) of mutant p53-E2F1 on ID4 promoter; RNA immunoprecipitation (RIP) and mRNA stability assays for IL8/GRO-alpha; siRNA knockdown of mutant p53; angiogenesis assays Nature structural & molecular biology High 19783986
2009 Ectopic Id4 expression in DU145 prostate cancer cells increases apoptosis and decreases proliferation (S-phase arrest), associated with increased androgen receptor (AR), p21, p27, and p53 expression; Id4 promoter is hypermethylated in DU145 cells. Ectopic expression by transfection, cell cycle analysis (3H-thymidine, FACS), RT-PCR, real-time PCR, Western blot, immunocytochemistry, MSP BMC cancer Medium 19500415
2010 ID4 is required for adipocyte differentiation: Id4-/- mice have reduced body fat; MEFs from Id4-/- mice have reduced adipogenic potential with decreased C/EBPα and PPARγ expression; ID4 is induced during 3T3-L1 adipocyte differentiation. Id4-knockout mouse analysis, MEF isolation and adipogenic differentiation assay, Western blot for C/EBPα and PPARγ The Journal of biological chemistry High 20460371
2010 Id4 promotes osteoblast differentiation via an Id4-Hes1-Hey2 mechanism: Id4 releases Hes1 from Hes1-Hey2 repressor complexes, and free Hes1 increases stability and transcriptional activity of Runx2, a key osteoblast differentiation factor. Loss of Id4 (Id4-/- mice) drastically reduces osteoblast differentiation and drives MSC differentiation toward adipocytes instead. Id4-knockout mouse analysis, ST2 cell line Id4 knockdown, genome-wide expression analysis, co-immunoprecipitation for Hes1-Hey2 interaction, Runx2 activity assays PLoS genetics High 20628571
2011 ID4 enhances SOX2 protein expression by suppressing miR-9* (which targets SOX2 3'-UTR), leading to SOX2-mediated induction of ABC transporters ABCC3 and ABCC6 and chemoresistance in glioma stem-like cells. shRNA knockdown, microRNA overexpression, luciferase 3'-UTR reporter assay, RT-PCR, Western blot, drug resistance assay Cancer research High 21531766
2011 ID4 regulates mammary gland ductal expansion by suppressing p38MAPK activity; p38MAPK is activated in Id4-null mammary cells and after siRNA-mediated knockdown; this p38MAPK activation is required for the reduced proliferation and increased apoptosis in Id4-ablated mammary glands. Id4-knockout mouse mammary analysis, siRNA knockdown in transformed mammary cells, p38MAPK phosphorylation Western blot, p38MAPK inhibitor treatment Development (Cambridge, England) High 22069192
2013 Id4 interacts directly with Twist1 (a bHLH transcription factor) to suppress Twist1-mediated MMP2 expression, thereby inhibiting invasiveness of glioblastoma cells; Id4 expression inversely correlates with MMP2 in GBM patient data. Co-immunoprecipitation of Id4 with Twist1, MMP2 reporter assay, invasion assay, siRNA knockdown, TCGA bioinformatic correlation Oncogene Medium 24413082
2013 ID4 forms a physical complex with mutant p53 and the acetyltransferase CBP/p300, resulting in acetylation of mutant p53 at K373; this acetylation restores mutant p53 DNA binding and transcriptional activity (BAX, PUMA, p21 expression and apoptosis). Loss of ID4 in LNCaP cells abrogates wild-type p53 DNA binding. Co-immunoprecipitation of ID4-p53-CBP/p300 complex, p53 acetylation Western blot, EMSA for p53 DNA binding, luciferase reporter for p53 transcriptional activity, apoptosis assay Molecular cancer High 24330748
2014 ID4 is a transcriptional target of gain-of-function p53 mutants (R175H, R273H, R280K); the mutant p53-E2F1 protein complex assembles on the ID4 promoter and positively controls ID4 expression. (Note: this finding was established in 2009; the 2014 review paper [PMID:25512197] elaborates on this but the original data is from PMID:19783986.) ChIP, reporter assay, siRNA depletion of mutant p53 Proceedings of the National Academy of Sciences of the United States of America High 19783986
2014 EZH2-dependent H3K27me3 initiates ID4 promoter silencing in prostate cancer; EZH2 and H3K27me3 are enriched at the ID4 promoter along with DNMT1 in ID4-negative cell lines; EZH2 knockdown in DU145 leads to re-expression of ID4 with concomitant loss of EZH2, H3K27me3, and DNMT1 at the promoter. Chromatin immunoprecipitation (ChIP) for EZH2, H3K27me3, DNMT1 on ID4 promoter; siRNA knockdown of EZH2; RT-PCR for ID4 re-expression Oncotarget High 25115397
2014 ID4 heterodimerizes with ID1, ID2, and ID3 via its HLH domain, acting as an inhibitor of inhibitors; ID4 promotes E47 (bHLH) DNA binding by sequestering ID1 (demonstrated by EMSA); the N-terminal alanine-stretch unique to ID4's HLH domain is required for optimal ID-ID interaction; ID4 and ID1 co-localize in prostate cancer cells. Co-immunoprecipitation, EMSA (electrophoretic mobility shift assay) for E47 DNA binding competition, co-localization by immunofluorescence, domain deletion mutagenesis Biochimie High 25778840
2014 Id4 acts as a downstream target of Notch2 signaling and maintains hippocampal neural stem cell (NSC) quiescence; Id4 knockdown rescues Notch2-induced inhibition of NSC proliferation; Id4 deletion activates NSC proliferation in the dentate gyrus without evoking neurogenesis; Id4 overexpression increases NSC maintenance and promotes astrogliogenesis at the expense of neurogenesis. Conditional Id4 knockout, lentiviral shRNA knockdown, Notch2 gain-of-function, BrdU proliferation assay, immunofluorescence, neurosphere assay Cell reports High 31390563
2014 Id4 chromatin immunoprecipitation confirmed Id4 binding to the Esr1 and Foxa1 promoter regions in mammary cells; Id4 deficiency leads to striking increases in ERα (Esr1), PR, and FoxA1 expression in both basal and luminal mammary subsets, indicating that Id4 is a negative transcriptional regulator of the ERα signaling axis. Conditional MMTV-Cre/K14-Cre Id4 knockout mouse model, ChIP for Id4 on Esr1/Foxa1 promoters, RT-PCR/Western blot for target gene expression Development (Cambridge, England) High 25038044
2014 Loss of ID4 in LNCaP prostate cancer cells (L-ID4) promotes castration-resistant prostate cancer (CRPC) through constitutive AR activation and de novo steroidogenesis; RNA-seq revealed a gene expression signature mimicking constitutively active AR in L-ID4 cells; PSA expression persisted in castrated conditions in L-ID4 but not control cells. Stable shRNA silencing of ID4 in LNCaP, RNA-seq, xenograft in castrated vs. non-castrated mice, PSA expression assay Molecular endocrinology High 24921661
2015 ID4 controls mammary stem cell self-renewal by suppressing key factors required for luminal differentiation; in an ID4-GFP knock-in reporter mouse, ID4 marks a stem cell-enriched basal mammary cell subset; single-cell transcriptomics revealed ID4-high cells have a distinct stem cell transcriptional signature. ID4-GFP knock-in reporter mouse, single-cell transcriptomics, FACS, mammary reconstitution assay Nature communications High 25813983
2016 ID4 directly interacts with FKBP52 (FK506-binding protein 52) in vitro (but not directly with AR); loss of ID4 increases FKBP52-dependent AR transcriptional activity and promotes CRPC; pharmacological inhibition of FKBP52-AR signaling with MJC13 attenuates tumor growth in L-ID4 xenografts. Proteomic analysis (proteomics of L-ID4 vs. L+ns), co-immunoprecipitation/protein interaction studies for ID4-FKBP52, in vitro binding assay, AR reporter assay, MJC13 pharmacological inhibition in xenograft Molecular oncology High 28252832
2017 Mutant p53 and ID4 delocalize lncRNA MALAT1 from nuclear speckles and favor its association with chromatin by recruiting MALAT1 via splicing factor SRSF1; this enables aberrant recruitment of MALAT1 on VEGFA pre-mRNA and modulation of VEGFA isoform expression in breast cancer cells. RNA immunoprecipitation (RIP), co-immunoprecipitation, RNA FISH for MALAT1 localization, VEGFA isoform analysis by RT-PCR, shRNA knockdown EMBO reports High 28652379
2017 ID4 level dictates spermatogonial stem cell (SSC) vs. progenitor state: the ID4-EGFPBright population functions as SSCs, whereas ID4-EGFPDim cells are transitioning to progenitors; conditional overexpression of Id4 blocks transition from SSC to progenitor state. Id4-eGFP reporter mouse, conditional Id4 overexpression mouse model, RNA-seq, FACS, transplantation assay Development (Cambridge, England) High 28087628
2017 ID4 regulates wild-type and mutant p53 transcriptional activity by promoting acetylation at K373 (and to a lesser extent K320) via CBP/p300 interaction; acetylation-mimic (K373Q) and non-acetylation mimic (K373R) p53 mutants confirmed K373 as the critical residue mediating ID4-dependent p53 activation and downstream cell cycle arrest/apoptosis. Ectopic expression in p53-null prostate cancer cells, acetylation-mimic/non-mimic p53 mutants, p53 DNA-binding assay, target gene expression (RT-PCR, Western blot), apoptosis/cell cycle assay Oncotarget High 27911860
2019 Id4 promotes elimination of the pro-activation bHLH factor Ascl1 protein in hippocampal neural stem cells (NSCs) by sequestering Ascl1's heterodimerization partner E47, thereby promoting Ascl1 protein degradation and maintaining NSC quiescence; Id4 deletion causes abnormal Ascl1 protein accumulation and premature stem cell activation. Id4 conditional knockout in adult hippocampus, Id4 overexpression in NSC cultures, Ascl1 protein level analysis by Western blot, E47-Ascl1-Id4 interaction studies by Co-IP, BrdU proliferation assay eLife High 31552825
2020 ID4 interacts with mediator of DNA damage checkpoint protein 1 (MDC1) and, through MDC1, also with DNA repair proteins γH2AX and BRCA1 at fragile chromatin sites; ID4 binds to chromatin following DNA damage but does not affect transcription at these sites, suggesting a role in DNA damage response rather than transcription per se. RIME (Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins), ChIP-seq, RNA-seq, immunoprecipitation Breast cancer research : BCR High 32527287
2021 ID4 interacts with the bHLH protein HEB (detected by mass spectrometry); ID4 antagonizes HEB transcriptional activity, preventing HEB from binding E-box motifs in regulatory elements of myoepithelial developmental genes (extracellular matrix, contractile cytoskeleton); loss of ID4 in mammary organoids/in vivo allows HEB-dependent myoepithelial differentiation. Mass spectrometry (proteomics) for ID4 interactome, ChIP-seq for HEB genomic binding, mammary organoid culture, conditional Id4 knockout mouse, RNA-seq iScience High 33554073
2021 CRISPR/dCas9-DNMT3a-targeted methylation of the Id2 and Id4 promoters drives oligodendrocyte precursor cell (OPC) differentiation, confirming that DNA methylation-mediated suppression of ID4 (and ID2) is a direct epigenetic mechanism controlling OPC differentiation. Epigenetic editing with CRISPR/dCas9-DNMT3a for targeted methylation of Id4 promoter, OPC differentiation assay Cellular and molecular life sciences : CMLS High 34482420
2024 ID4 expression in breast cancer cells promotes VEGFA secretion, which stimulates VEGFR2-integrin β3 interaction in a paracrine fashion; this interaction activates the focal adhesion pathway, promotes migration/invasion/stress fiber formation, and drives nuclear translocation and activation of YAP and TAZ. Overexpression and knockdown of ID4, conditioned media paracrine experiments, co-immunoprecipitation of VEGFR2-integrin β3, VEGFA ELISA, YAP/TAZ nuclear localization assay, invasion/migration assay Cell death & disease Medium 38321003

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2001 Identification of Id4 as a regulator of BRCA1 expression by using a ribozyme-library-based inverse genomics approach. Proceedings of the National Academy of Sciences of the United States of America 180 11136250
2014 Functional and molecular features of the Id4+ germline stem cell population in mouse testes. Genes & development 178 24939937
2000 The Id4 HLH protein and the timing of oligodendrocyte differentiation. The EMBO journal 175 10790366
2011 ID4 imparts chemoresistance and cancer stemness to glioma cells by derepressing miR-9*-mediated suppression of SOX2. Cancer research 172 21531766
2009 The execution of the transcriptional axis mutant p53, E2F1 and ID4 promotes tumor neo-angiogenesis. Nature structural & molecular biology 169 19783986
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
2017 ID4 levels dictate the stem cell state in mouse spermatogonia. Development (Cambridge, England) 155 28087628
2005 Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia. Nature genetics 147 15723065
2012 Targeted tumor-penetrating siRNA nanocomplexes for credentialing the ovarian cancer oncogene ID4. Science translational medicine 137 22896676
2004 Id4 regulates neural progenitor proliferation and differentiation in vivo. Development (Cambridge, England) 102 15469968
2017 The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1. EMBO reports 92 28652379
2003 Downregulation of ID4 by promoter hypermethylation in gastric adenocarcinoma. Oncogene 83 14534543
2019 Id4 Downstream of Notch2 Maintains Neural Stem Cell Quiescence in the Adult Hippocampus. Cell reports 81 31390563
2008 Cdc42 is highly expressed in colorectal adenocarcinoma and downregulates ID4 through an epigenetic mechanism. International journal of oncology 80 18575765
2005 Aberrant hypermethylation of ID4 gene promoter region increases risk of lymph node metastasis in T1 breast cancer. Oncogene 80 15897910
2006 Inhibitors of differentiation (ID1, ID2, ID3 and ID4) genes are neuronal targets of MeCP2 that are elevated in Rett syndrome. Human molecular genetics 79 16682435
2019 LncRNA SNHG7 promotes pancreatic cancer proliferation through ID4 by sponging miR-342-3p. Cell & bioscience 76 30949340
2006 Multiple roles of Id4 in developmental myelination: predicted outcomes and unexpected findings. Glia 74 16862533
2019 Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells. eLife 69 31552825
2005 Id4 is required for the correct timing of neural differentiation. Developmental biology 69 15882580
2015 Id4 Marks Spermatogonial Stem Cells in the Mouse Testis. Scientific reports 65 26621350
2010 Id4, a new candidate gene for senile osteoporosis, acts as a molecular switch promoting osteoblast differentiation. PLoS genetics 65 20628571
2008 Promoter methylation-associated loss of ID4 expression is a marker of tumour recurrence in human breast cancer. BMC cancer 65 18513385
1995 Mutually exclusive expression of two dominant-negative helix-loop-helix (dnHLH) genes, Id4 and Id3, in the developing brain of the mouse suggests distinct regulatory roles of these dnHLH proteins during cellular proliferation and differentiation of the nervous system. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 61 7547505
2009 Inhibitor of differentiation 4 (Id4) is a potential tumor suppressor in prostate cancer. BMC cancer 60 19500415
2010 Silencing of the inhibitor of DNA binding protein 4 (ID4) contributes to the pathogenesis of mouse and human CLL. Blood 59 21098398
2014 miR-342 regulates BRCA1 expression through modulation of ID4 in breast cancer. PloS one 58 24475217
2014 Inhibitor of differentiation 4 (ID4): From development to cancer. Biochimica et biophysica acta 58 25512197
2001 Hormonal regulation and differential actions of the helix-loop-helix transcriptional inhibitors of differentiation (Id1, Id2, Id3, and Id4) in Sertoli cells. Endocrinology 55 11316735
2015 ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype. Nature communications 53 25813983
2014 Id4 suppresses MMP2-mediated invasion of glioblastoma-derived cells by direct inactivation of Twist1 function. Oncogene 52 24413082
1995 Molecular cloning of ID4, a novel dominant negative helix-loop-helix human gene on chromosome 6p21.3-p22. Genomics 52 7665172
2003 Cloning and characterization of Xenopus Id4 reveals differing roles for Id genes. Developmental biology 51 14651922
2014 EZH2 dependent H3K27me3 is involved in epigenetic silencing of ID4 in prostate cancer. Oncotarget 50 25115397
2005 Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer. Molecular cancer 50 15876350
2007 t(6;14)(p22;q32): a new recurrent IGH@ translocation involving ID4 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Blood 46 17940204
1999 Id4 expression induces apoptosis in astrocytic cultures and is down-regulated by activation of the cAMP-dependent signal transduction pathway. Experimental cell research 44 10066362
2017 Epigenetic dysregulation of ID4 predicts disease progression and treatment outcome in myeloid malignancies. Journal of cellular and molecular medicine 43 28452111
2006 Id proteins expression in prostate cancer: high-level expression of Id-4 in primary prostate cancer is associated with development of metastases. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 42 16575399
2018 Expression of ID4 protein in breast cancer cells induces reprogramming of tumour-associated macrophages. Breast cancer research : BCR 39 29921315
2006 Tumoral expression of BRCA1, estrogen receptor alpha and ID4 protein in patients with sporadic breast cancer. Cancer biology & therapy 38 16582598
2011 ID4 regulates mammary gland development by suppressing p38MAPK activity. Development (Cambridge, England) 37 22069192
2021 DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation. Cellular and molecular life sciences : CMLS 36 34482420
1998 A role for Sp and helix-loop-helix transcription factors in the regulation of the human Id4 gene promoter activity. The Journal of biological chemistry 34 9516472
2010 ID4: a new player in the cancer arena. Oncotarget 33 21293053
2003 Id4 regulates mammary epithelial cell growth and differentiation and is overexpressed in rat mammary gland carcinomas. The American journal of pathology 33 14633621
2001 Id4 expression and its relationship to other Id genes during avian embryonic development. Mechanisms of development 33 11731247
2016 Just a Flexible Linker? The Structural and Dynamic Properties of CBP-ID4 Revealed by NMR Spectroscopy. Biophysical journal 32 26789760
2003 Id4 is deregulated by a t(6;14)(p22;q32) chromosomal translocation in a B-cell lineage acute lymphoblastic leukemia. Haematologica 32 12969807
2014 Dual roles for Id4 in the regulation of estrogen signaling in the mammary gland and ovary. Development (Cambridge, England) 31 25038044
2015 Inhibitor of differentiation 4 (ID4) acts as an inhibitor of ID-1, -2 and -3 and promotes basic helix loop helix (bHLH) E47 DNA binding and transcriptional activity. Biochimie 30 25778840
2013 Id4 dependent acetylation restores mutant-p53 transcriptional activity. Molecular cancer 30 24330748
2020 UVB induces cutaneous squamous cell carcinoma progression by de novo ID4 methylation via methylation regulating enzymes. EBioMedicine 29 32574963
2014 Evaluation of candidate spermatogonial markers ID4 and GPR125 in testes of adult human cadaveric organ donors. Andrology 28 24902969
2006 Id4 messenger RNA and estrogen receptor expression: inverse correlation in human normal breast epithelium and carcinoma. Human pathology 28 16867866
2013 Id2, Id3 and Id4 overcome a Smad7-mediated block in tumorigenesis, generating TGF-β-independent melanoma. Carcinogenesis 27 24343358
2012 Id4 protein is highly expressed in triple-negative breast carcinomas: possible implications for BRCA1 downregulation. Breast cancer research and treatment 27 22538771
2010 Inhibitor of DNA binding 4 (ID4) regulation of adipocyte differentiation and adipose tissue formation in mice. The Journal of biological chemistry 26 20460371
2007 Frequent DNA methylation but not mutation of the ID4 gene in malignant lymphoma. Journal of clinical and experimental hematopathology : JCEH 26 17510533
2022 Mesenchymal stem cell-derived exosome mir-342-3p inhibits metastasis and chemo-resistance of breast cancer through regulating ID4. Genes & genomics 25 35023068
2012 Epigenetic inactivation of inhibitor of differentiation 4 (Id4) correlates with prostate cancer. Cancer medicine 25 23342267
2010 Increased inhibitor of differentiation 4 (id4) expression in glioblastoma: a tissue microarray study. Journal of Cancer 25 20842217
2009 Differential methylation pattern of ID4, SFRP1, and SHP1 between acute myeloid leukemia and chronic myeloid leukemia. Journal of Korean medical science 24 19543515
1999 Expression of the dominant-negative regulator Id4 is induced during adipocyte differentiation. Biochemical and biophysical research communications 23 10080947
2011 ID4 is frequently downregulated and partially hypermethylated in prostate cancer. World journal of urology 22 21882048
2009 ID4 methylation predicts high risk of leukemic transformation in patients with myelodysplastic syndrome. Leukemia research 22 19853913
2018 Epigenetic regulation of ID4 in breast cancer: tumor suppressor or oncogene? Clinical epigenetics 20 30139383
2005 Id4 and FABP7 are preferentially expressed in cells with astrocytic features in oligodendrogliomas and oligoastrocytomas. BMC clinical pathology 20 16018821
2019 JNK inactivation suppresses osteogenic differentiation, but robustly induces osteopontin expression in osteoblasts through the induction of inhibitor of DNA binding 4 (Id4). FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19 30884976
2019 MicroRNA-335/ID4 dysregulation predicts clinical outcome and facilitates leukemogenesis by activating PI3K/Akt signaling pathway in acute myeloid leukemia. Aging 19 31147526
2017 Astrocytes induce proliferation of oligodendrocyte progenitor cells via connexin 47-mediated activation of the ERK/Id4 pathway. Cell cycle (Georgetown, Tex.) 19 28278052
2013 Id4 deficiency attenuates prostate development and promotes PIN-like lesions by regulating androgen receptor activity and expression of NKX3.1 and PTEN. Molecular cancer 19 23786676
2015 Increased ID4 expression, accompanied by mutant p53 accumulation and loss of BRCA1/2 proteins in triple-negative breast cancer, adversely affects survival. Histopathology 18 26259780
2013 Id4 promotes senescence and sensitivity to doxorubicin-induced apoptosis in DU145 prostate cancer cells. Anticancer research 18 24122992
2016 Id4 promotes cisplatin resistance in lung cancer through the p38 MAPK pathway. Anti-cancer drugs 17 27537399
2014 Inhibitor of differentiation 4 (ID4) inactivation promotes de novo steroidogenesis and castration-resistant prostate cancer. Molecular endocrinology (Baltimore, Md.) 17 24921661
2021 miR-9-5p Promotes Lung Adenocarcinoma Cell Proliferation, Migration and Invasion by Targeting ID4. Technology in cancer research & treatment 16 34723712
2011 The effect of adjuvants on the immune response induced by a DBL4ɛ-ID4 VAR2CSA based Plasmodium falciparum vaccine against placental malaria. Vaccine 14 22122859
2021 ID1 and ID4 Are Biomarkers of Tumor Aggressiveness and Poor Outcome in Immunophenotypes of Breast Cancer. Cancers 13 33514024
2020 Paracrine Signaling from Breast Cancer Cells Causes Activation of ID4 Expression in Tumor-Associated Macrophages. Cells 13 32054109
2017 Expression and regulation of inhibitor of DNA binding proteins ID1, ID2, ID3, and ID4 at the maternal-conceptus interface in pigs. Theriogenology 13 29197292
2016 ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells. Biochemical and biophysical research communications 13 27462022
2011 ID4 mediates proliferation of astrocytes after excitotoxic damage in the mouse hippocampus. Anatomy & cell biology 13 21829756
2022 Upregulated circTMEM59 Inhibits Cell Growth and Metastasis by miR-668-3p/ID4 Axis in Colorectal Cancer. Oxidative medicine and cellular longevity 12 35656024
2021 Inhibitor of Differentiation 4 (ID4) represses mammary myoepithelial differentiation via inhibition of HEB. iScience 12 33554073
2019 MicroRNA-188-5p Promotes Epithelial-Mesenchymal Transition by Targeting ID4 Through Wnt/β‑catenin Signaling in Retinoblastoma. OncoTargets and therapy 12 31819510
2017 Id4 promotes cell proliferation in hepatocellular carcinoma. Chinese journal of cancer 12 28143562
2017 Inactivation of ID4 promotes a CRPC phenotype with constitutive AR activation through FKBP52. Molecular oncology 12 28252832
2015 Epigenetic regulation of ID4 in the determination of the BRCAness phenotype in breast cancer. Breast cancer research and treatment 12 26610810
2008 Id2, Id3, and Id4 proteins show dynamic changes in expression during vibrissae follicle development. Developmental dynamics : an official publication of the American Association of Anatomists 12 18498089
1998 cDNA cloning, tissue distribution and chromosomal localization of the human ID4 gene. DNA research : an international journal for rapid publication of reports on genes and genomes 12 9872455
2024 ID4-dependent secretion of VEGFA enhances the invasion capability of breast cancer cells and activates YAP/TAZ via integrin β3-VEGFR2 interaction. Cell death & disease 11 38321003
2022 miR-210-3p protects against osteoarthritis through inhibiting subchondral angiogenesis by targeting the expression of TGFBR1 and ID4. Frontiers in immunology 11 36263050
2019 MiR-342-3p inhibition promotes cell proliferation and invasion by directly targeting ID4 in pre-eclampsia. The journal of obstetrics and gynaecology research 11 31749272
1998 Structure, chromosomal localisation and expression of the murine dominant negative helix-loop-helix Id4 gene. Biochimica et biophysica acta 11 9838043
2021 Id2 and Id4 are not the major negative regulators of oligodendrocyte differentiation during early central nervous system development. Glia 10 34889481
2020 Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer. Breast cancer research : BCR 10 32527287
2017 ID4 regulates transcriptional activity of wild type and mutant p53 via K373 acetylation. Oncotarget 10 27911860
1998 The mouse Id2 and Id4 genes: structural organization and chromosomal localization. Gene 10 9831657

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