Affinage

ID2

DNA-binding protein inhibitor ID-2 · UniProt Q02363

Length
134 aa
Mass
14.9 kDa
Annotated
2026-04-28
100 papers in source corpus 42 papers cited in narrative 42 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ID2 is a helix-loop-helix (HLH) protein that lacks a basic DNA-binding domain and functions as a dominant-negative inhibitor of basic HLH (bHLH) transcription factors and Rb-family tumor suppressors, thereby controlling cell proliferation, differentiation, and lineage commitment across diverse tissues including the immune, nervous, cardiovascular, and intestinal systems. ID2 heterodimerizes with E-proteins (E47, E2A) to block their DNA-binding activity and downstream target gene expression—including p57Kip2, Socs3, SEMA3F, and Tcf7—while also directly binding and neutralizing pRb, p107, and p130 to promote cell-cycle progression (PMID:1922066, PMID:8649364, PMID:16705184, PMID:26795246). ID2 protein stability is tightly regulated by APC/C(Cdh1)-dependent D-box-mediated degradation in neurons, N-terminal ubiquitination, ASB4 E3 ligase activity in trophoblasts, USP1-mediated deubiquitination in glioma, and CDK2-dependent phosphorylation that relieves bHLH inhibition in late G1 (PMID:16810178, PMID:14733935, PMID:24586788, PMID:26951930, PMID:9029153). ID2 transcription is activated by Myc, β-catenin/TCF4, HIF-1, C/EBPβ, BMP/Smad, and Nkx2-5/Tbx5, and repressed by TGF-β (via Mad-Max promoter switching), p53, Bcl6, Mtg16, and Ovol1, integrating multiple developmental and stress signals into a single dominant-negative output (PMID:11034201, PMID:11572874, PMID:15252039, PMID:15809228, PMID:12824180, PMID:21608079, PMID:27213691).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1991 High

    Establishing that ID2 is an HLH-only protein that heterodimerizes with and inhibits specific bHLH transcription factors resolved how a protein lacking a DNA-binding domain could function as a transcriptional regulator.

    Evidence In vitro binding and DNA-binding inhibition assays with cloned Id2 against multiple bHLH proteins

    PMID:1922066

    Open questions at the time
    • Structural basis of selective partner recognition unknown
    • In vivo relevance not yet demonstrated
    • Full spectrum of bHLH partners not mapped
  2. 1995 Medium

    Identification that bHLH factors activate the Id2 promoter through E-boxes, and that Id2 blocks this activation, revealed a negative autoregulatory feedback loop governing Id2 expression levels.

    Evidence Reporter/luciferase promoter assay with co-expression in F9 cells

    PMID:7589553

    Open questions at the time
    • Direct E-box binding by bHLH factors at the endogenous Id2 promoter not confirmed by ChIP
    • Physiological significance of the feedback loop not tested in vivo
  3. 1996 High

    Demonstrating that ID2 uniquely among Id family members directly binds and neutralizes all three Rb-family pocket proteins established a second major mechanism—beyond bHLH inhibition—by which ID2 promotes cell-cycle progression.

    Evidence In vitro binding assays, co-immunoprecipitation in Saos-2 cells, and cell-cycle arrest rescue assays

    PMID:8649364

    Open questions at the time
    • Structural basis of ID2–Rb interaction unknown
    • Whether Rb binding and bHLH binding are mutually exclusive or concurrent was not resolved
  4. 1997 High

    Showing that cyclin E–CDK2 and cyclin A–CDK2 phosphorylate ID2 in late G1, correlating with restoration of E-box-dependent transcription, established a cell-cycle-dependent mechanism that inactivates ID2's inhibitory function.

    Evidence In vitro kinase assays with purified cyclin–CDK complexes; in vivo phosphorylation in synchronized fibroblasts; EMSA

    PMID:9029153

    Open questions at the time
    • Precise phosphorylation site mutant analysis not reported in this study
    • Whether phosphorylation also affects Rb binding was not tested
  5. 2000 High

    Genetic epistasis showing that Id2–Rb double-knockout embryos survive to term, combined with evidence that Myc directly activates Id2 transcription, placed ID2 as a critical mediator in the Myc→ID2⊣Rb oncogenic pathway.

    Evidence Double-knockout rescue in mice; quantitative protein analysis; neuroblastoma cell analysis

    PMID:11034201

    Open questions at the time
    • Whether this axis operates equivalently in all Myc-driven cancers was not established
    • Contribution of ID2's bHLH-inhibitory function versus Rb-inhibitory function in this pathway not disentangled
  6. 2001 High

    Identification of β-catenin/TCF4 as a direct transcriptional activator of ID2 via a TCF4-binding motif linked ID2 to canonical Wnt signaling and anchorage-independent survival in colon cancer.

    Evidence EMSA, supershift, site-directed mutagenesis of TCF4 site, reporter assay in colon carcinoma cells

    PMID:11572874

    Open questions at the time
    • ChIP confirmation of endogenous TCF4 occupancy at the Id2 promoter not performed
    • Downstream effectors of ID2 in anchorage-independent survival not identified
  7. 2003 High

    Discovering that TGF-β represses Id2 via Mad-Max promoter switching and that TGF-β also induces Id2 in dendritic cell precursors revealed context-dependent transcriptional regulation of Id2, with TGF-β repressing Id2 in epithelial cells to enable cytostasis but inducing it in immune progenitors to control DC lineage choice.

    Evidence ChIP showing Myc-Max to Mad-Max switch at Id2 promoter in epithelial cells; Id2-KO mouse DC analysis with TGF-β stimulation

    PMID:12598895 PMID:12824180

    Open questions at the time
    • Molecular basis of context-dependent TGF-β regulation (repression vs. activation) not resolved
    • Whether Smad proteins directly bind the Id2 promoter in DC progenitors was not shown
  8. 2004 High

    Demonstrating that ID2 is degraded via N-terminal ubiquitination (conjugation to the α-NH2 group rather than internal lysines) and that the first 15 N-terminal residues serve as an E3 recognition element revealed an unconventional proteolytic control mechanism, while HIF-1 was shown to directly activate Id2 transcription under hypoxia.

    Evidence Lysine-less mutant degradation assays and N-terminal tagging stabilization experiments; ChIP and EMSA identifying HIF-1 binding sites in the Id2 promoter

    PMID:14733935 PMID:15252039

    Open questions at the time
    • The specific E3 ligase mediating N-terminal ubiquitination was not identified
    • Physiological relevance of HIF-1–Id2 axis beyond neuroblastoma not explored
  9. 2005 High

    C/EBPβ was identified as a direct transcriptional activator of Id2 via ChIP-confirmed promoter occupancy, while Ovol1 was shown to repress Id2 in spermatocytes, and polycystin-2 (PC2) was found to physically interact with ID2 in a phosphorylation-dependent manner relevant to cystic kidney disease.

    Evidence ChIP, EMSA, mutagenesis, and C/EBPβ-null mammary analysis; Ovol1-KO mouse spermatocyte analysis; PC2 co-immunoprecipitation and RNAi rescue in PKD cells

    PMID:15716349 PMID:15809228 PMID:16311606

    Open questions at the time
    • Direct mechanism by which PC2 sequesters ID2 not structurally resolved
    • Whether PC2–ID2 interaction is relevant beyond cystic kidney disease not tested
  10. 2006 High

    Multiple discoveries converged to show how ID2 protein is spatially and temporally controlled: APC/C(Cdh1) targets ID2 for D-box-dependent degradation in post-mitotic neurons (controlling axon growth via Nogo receptor), ENH sequesters ID2 in the cytoplasm during differentiation, and E47–ID2 antagonism regulates p57Kip2 in neuroblastoma, building a comprehensive picture of multi-layered ID2 regulation in neural cells.

    Evidence D-box mutagenesis and APC/C interaction assays with in vivo axon growth readout; ENH co-IP with bidirectional manipulation and subcellular localization; E47-driven p57Kip2 reporter with RNAi rescue

    PMID:16549780 PMID:16705184 PMID:16810178

    Open questions at the time
    • Whether APC/C(Cdh1) and ENH pathways cooperate or act independently not addressed
    • Whether p57Kip2 is the sole E-protein target mediating cell-cycle arrest in neural progenitors unknown
  11. 2007 High

    Placing Id2 downstream of the cardiac transcription factors Nkx2-5 and Tbx5 in ventricular conduction system specification broadened ID2's developmental role beyond immune and neural tissues to cardiac morphogenesis.

    Evidence Id2 promoter reporter in vivo; compound haploinsufficiency genetic epistasis in mouse heart

    PMID:17604724

    Open questions at the time
    • Direct bHLH targets of ID2 in conduction system cells not identified
    • Whether ID2 acts via Rb or bHLH inhibition in this context not resolved
  12. 2010 High

    BMP/Smad-binding elements in the Id2 promoter were biochemically mapped, and ID2 was shown to promote tumor cell migration by repressing SEMA3F through E47 antagonism, linking ID2 to invasion beyond its established role in proliferation.

    Evidence ChIP and EMSA for Smad binding at Id2 promoter; E-box mutagenesis at SEMA3F promoter with migration/invasion assays

    PMID:20388805 PMID:20674548

    Open questions at the time
    • In vivo validation of SEMA3F-dependent invasion pathway not performed
    • Whether other semaphorins are similarly regulated by E47/ID2 not tested
  13. 2011 High

    Demonstrating that p53 directly represses Id2 transcription established ID2 as a node integrating tumor-suppressor and oncogenic signals: Myc activates and p53 represses the same gene, with the balance determining neural progenitor proliferation.

    Evidence ChIP for p53 at Id2 promoter; Id2 knockdown rescue in p53-null NPCs

    PMID:21608079

    Open questions at the time
    • Whether p53-mediated Id2 repression operates in non-neural tissues not addressed
    • Mechanism by which p53 binding leads to transcriptional repression not dissected
  14. 2013 High

    Showing that ID2 restrains CD8+ T-cell memory differentiation by blocking E2A-mediated Tcf7 (TCF1) activation established ID2 as a molecular switch between effector and memory T-cell fates.

    Evidence Id2-KO CD8+ T-cell analysis during infection; E2A binding site reporter assay; gene expression profiling

    PMID:23536629

    Open questions at the time
    • Whether ID2 affects TCF1 protein stability in addition to transcription not tested
    • Relative contribution of ID2 versus ID3 in memory/effector balance not resolved
  15. 2014 High

    Identification of ASB4 as an E3 ubiquitin ligase that targets ID2 for proteasomal degradation in trophoblasts provided a tissue-specific degradation mechanism controlling vascular differentiation in the placenta.

    Evidence Direct ubiquitination assay; degradation-resistant ID2 mutant; Asb4-null mouse placenta analysis

    PMID:24586788

    Open questions at the time
    • Whether ASB4 ubiquitinates ID2 at the N-terminus or at lysine residues not determined
    • Relationship between ASB4 and APC/C(Cdh1)-mediated degradation pathways not examined
  16. 2016 High

    Three concurrent advances revealed that: USP1 deubiquitinase stabilizes ID2 to drive glioma survival (PDGF–E2F–USP1–ID2 axis); ID2 controls NK cell homeostasis by repressing E-protein target Socs3; and Bcl6 represses Id2 to promote TFH over TH1 differentiation, firmly establishing ID2 as a central integrator of immune lineage decisions.

    Evidence USP1 pharmacologic inhibition and Id2 KO in glioma model with ChIP; Id2 conditional KO in NK cells with Socs3 double-KO epistasis; Bcl6 ChIP at Id2 locus with T-cell subset phenotyping

    PMID:26795246 PMID:26951930 PMID:27213691

    Open questions at the time
    • Whether USP1 deubiquitinates ID2 at the N-terminal ubiquitin or at lysine-linked chains not resolved
    • How Bcl6 mechanistically represses the Id2 locus (co-repressor identity) not identified
  17. 2019 High

    Genome-wide binding analysis of Mtg16 at the Id2 locus, combined with an Nfil3–Zeb2–Id2 genetic circuit controlling cDC1 specification, consolidated ID2 as the key node in a multi-factor transcriptional network governing dendritic cell lineage commitment.

    Evidence Mtg16 ChIP-seq with Id2/Mtg16 double-KO epistasis; scRNA-seq of CDPs with Nfil3/Zeb2/Id2 genetic epistasis

    PMID:24980046 PMID:31406377

    Open questions at the time
    • How Mtg16 mechanistically represses the Id2 promoter (direct or indirect DNA binding) not fully resolved
    • Whether the Nfil3–Zeb2–Id2 circuit operates in human DC development not confirmed
  18. 2020 High

    Structural and biochemical reconstitution of the monoubiquitinated FANCI–FANCD2 (ID2) complex showed that FANCD2 ubiquitination drives a conformational change enabling the complex to encircle DNA, clarifying the molecular basis of DNA interstrand crosslink repair activation (note: this concerns the FANCI–FANCD2 complex, distinct from the HLH protein ID2).

    Evidence Structural analysis of ubiquitinated ID2 complex; DNA-binding affinity assays; deubiquitination protection assays with USP1–UAF1

    PMID:32510829

    Open questions at the time
    • This finding pertains to the FANCI–FANCD2 heterodimer, not the HLH protein ID2; included here because both share the 'ID2' acronym in the literature
  19. 2021 High

    Demonstrating that TGF-β suppresses Id2 in developing airway basal stem cells and that persistent Id2 expression drives basal cell hyperplasia established the TGF-β–ID2 axis as a proliferation switch with precancerous implications, while ID2 was also shown to suppress TCF1 amplitude to control terminal NK cell maturation.

    Evidence Bidirectional genetic manipulation (Id2 OE, Tgfbr2 KO) in murine airways with scRNA-seq; Id2 conditional KO in NK cells with in vivo melanoma clearance assay

    PMID:33857289 PMID:34129836

    Open questions at the time
    • Whether TGF-β–ID2 axis directly causes malignant transformation or only a precancerous state not resolved
    • Mechanism by which ID2 suppresses TCF1 (direct E-protein sequestration vs. other) not fully dissected
  20. 2022 High

    E-cadherin loss was shown to de-repress Id2 via a p120-catenin/Kaiso pathway, with cytosolic ID2 inducing G0/G1 arrest through hypo-phosphorylated Rb interaction, unexpectedly demonstrating that ID2 can promote quiescence and anoikis resistance rather than proliferation depending on subcellular context.

    Evidence ChIP for Kaiso at Id2 promoter; co-IP of ID2 with Rb; subcellular fractionation; in vivo lung colonization assay in ILC models

    PMID:35437308

    Open questions at the time
    • How cytosolic ID2 preferentially binds hypo-phosphorylated Rb while nuclear ID2 antagonizes Rb growth suppression is paradoxical and not mechanistically reconciled
    • Generalizability beyond invasive lobular carcinoma not tested
  21. 2024 High

    Elucidating that ID2 disrupts a Tcf3–Tal1 complex to prevent LSD1 recruitment to the Slamf6 promoter, thereby maintaining permissive H3K4me2 marks, revealed an epigenetic mechanism through which ID2 sustains progenitor exhausted CD8+ T cells—extending its function beyond simple bHLH sequestration to chromatin remodeling.

    Evidence Co-IP of ID2 HLH domain with Tcf3; ChIP for H3K4me2 at Slamf6 promoter; LSD1 inhibitor rescue in Id2-KO tumor-bearing mice

    PMID:38287103

    Open questions at the time
    • Whether ID2-mediated disruption of LSD1 recruitment occurs at other loci genome-wide not tested
    • Direct structural basis of how ID2 HLH domain disrupts the Tcf3–Tal1 interface unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of ID2's selective partner recognition (bHLH vs. Rb vs. PC2); how nuclear vs. cytosolic ID2 exerts opposing effects on Rb-mediated cell-cycle control; the identity of the E3 ligase mediating N-terminal ubiquitination; and comprehensive mapping of the chromatin landscape changes driven by ID2 across immune and non-immune lineages.
  • No high-resolution structure of ID2 in complex with any partner
  • Nuclear vs. cytosolic ID2 function on Rb not mechanistically reconciled
  • Genome-wide ID2-dependent chromatin remodeling not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 7 GO:0140110 transcription regulator activity 5
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 8 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-1266738 Developmental Biology 3
Partners
ASB4CDH1E2AENHPU.1RB1TCF3USP1
Complex memberships
APC/C(Cdh1) (as substrate)

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Id2 contains a helix-loop-helix (HLH) dimerization motif but lacks the basic DNA-binding domain; it selectively heterodimerizes with and inhibits the DNA-binding activity of one class of bHLH transcription factors (e.g., E2A/E47, E2B/m3) but not another (TFE3, USF, AP4), and homodimerizes poorly. In vitro binding and DNA-binding inhibition assays; gene cloning and sequence analysis; chromosome mapping Molecular and cellular biology High 1922066
1996 Id2 (but not Id1 or Id3) directly binds pRb, p107, and p130 in vitro and in vivo, neutralizing their growth-suppressive activity and reversing cell-cycle arrest imposed by pRb family members and CDK inhibitors p16 and p21; Id2 expression also reduces cyclin D1 levels and cyclin D1–CDK4 complexes. In vitro binding assays; co-immunoprecipitation in transfected Saos-2 cells; cell-cycle arrest rescue assays; Western blot for cyclin D1 Molecular and cellular biology High 8649364
1997 Id2 is phosphorylated by cyclin E–CDK2 and cyclin A–CDK2 (but not cyclin D–CDKs) on a serine within a CDK consensus site in late G1; phosphorylation of Id2 in serum-stimulated fibroblasts correlates with restoration of E-box-dependent DNA-binding complexes, indicating that CDK-mediated phosphorylation relieves Id2-mediated inhibition of bHLH transcription factors. In vitro kinase assays with purified cyclin–CDK complexes; in vivo phosphorylation in synchronised human diploid fibroblasts; electrophoretic mobility shift assay (EMSA) The EMBO journal High 9029153
2000 Id2 is a direct transcriptional target of Myc-family oncoproteins; Id2 acts as a dominant-negative antagonist of Rb-family proteins; in neuroblastoma cells overexpressing N-Myc, Id2 is in molar excess of active Rb, and cell-cycle progression driven by Myc oncoproteins requires Id2-mediated inactivation of Rb. Id2–Rb double-knockout embryos survive to term, revealing a functional epistatic relationship. Genetic double-knockout rescue; quantitative protein analysis; transcriptional activation assays; neuroblastoma cell analysis Nature High 11034201
2004 Id2 is degraded by the ubiquitin–proteasome system via N-terminal ubiquitination: a Myc-tag fused to the N-terminus (but not C-terminus) stabilises Id2, lysine-less Id2 is still efficiently degraded (ubiquitin conjugated to α-NH2 group), and deletion of the first 15 N-terminal residues stabilises the protein, identifying this domain as an E3 recognition element. Ubiquitination assays; N-terminal tagging stabilisation experiments; lysine-less mutant degradation assays; proteasome inhibitor experiments Biochemical and biophysical research communications High 14733935
2005 Polycystin-2 (PC2) directly interacts with Id2; this interaction is regulated by PC1-dependent phosphorylation of PC2. Id2 expression suppresses p21 induction by PC1 or PC2, and Id2 shows enhanced nuclear localisation in cystic kidneys. RNAi knockdown of Id2 corrects the hyperproliferative phenotype of PC1-mutant cells. Co-immunoprecipitation; phosphorylation assays; RNAi knockdown with proliferation readout; immunofluorescence in human/mouse cystic kidney tissue Nature cell biology High 16311606
2006 APC/C(Cdh1) targets Id2 for proteasomal degradation through a conserved destruction box (D-box) motif in neurons. Id2 interacts with core APC/C subunits and Cdh1; D-box mutants of Id2 resist Cdh1 binding, remain stable after cell-cycle exit, and enhance axonal growth in cerebellar granule neurons in vitro and in vivo, overcoming myelin inhibitory signals. Degradation of Id2 permits accumulation of the Nogo receptor, a bHLH target gene product that inhibits axonal growth. Co-immunoprecipitation; APC/C interaction assays; D-box mutagenesis; cerebellar granule neuron axon growth assays in vitro and in vivo; gene expression analysis Nature High 16810178
2006 The actin-associated LIM-domain protein ENH (enigma homolog) is a cytoplasmic retention factor for Id2: ENH binds the HLH domain of Id2 in vitro and in vivo, its overexpression in neuroblastoma cells translocates Id2 from nucleus to cytoplasm and inactivates its transcriptional and cell-cycle-promoting functions, and RNAi silencing of ENH prevents cytoplasmic relocation of Id2 during retinoic acid-induced differentiation. Co-immunoprecipitation; in vitro binding assay; fluorescence microscopy of subcellular localisation; RNAi knockdown with localisation and functional readouts Proceedings of the National Academy of Sciences of the United States of America High 16549780
2006 Id2 prevents E-protein-mediated activation of p57Kip2 expression in neuroblastoma cells: E47 directly activates p57Kip2 transcription to block S-phase entry, Id2 suppresses this activation, and RNAi knockdown of p57Kip2 fully reverses E47-mediated cell-cycle arrest, establishing p57Kip2 as the functionally relevant CDK inhibitor target of the E-protein/Id2 axis in neural cells. Microarray gene expression profiling; reporter assays; RNAi knockdown; cell-cycle analysis Molecular and cellular biology High 16705184
2003 TGF-β induces Id2 expression in dendritic cell precursors; Id2 is required for development of Langerhans cells and splenic CD8α+ DCs, and Id2 represses B-cell lineage genes in DCs, establishing a TGF-β–Id2 signaling axis that controls DC lineage choice. Id2-knockout mouse analysis; in vitro DC differentiation with TGF-β stimulation; gene expression profiling Nature immunology High 12598895
2007 A 1.2 kb Id2 promoter fragment is cooperatively regulated by Nkx2-5 and Tbx5 in vitro and is sufficient for conduction-system-specific expression in vivo; compound haploinsufficiency of Tbx5 and Id2 (or Tbx5 and Nkx2-5) blocks embryonic specification of the ventricular conduction system, placing Id2 downstream of Tbx5/Nkx2-5 in a conduction system developmental pathway. SAGE transcriptional profiling; Id2-deficient mouse cardiac analysis; promoter reporter assay; compound haploinsufficiency genetic epistasis; in vivo transgenic reporter Cell High 17604724
2001 Id2 is a direct transcriptional target of β-catenin/TCF4; a TCF4-binding motif in the Id2 promoter is identified by EMSA and supershift, and site-directed mutagenesis abolishes promoter activity; β-catenin overexpression increases Id2 protein, and Id2 expression promotes anchorage-independent survival of colon carcinoma cells. Reporter assay; EMSA and supershift; site-directed mutagenesis; transfection; anchorage-independent growth assay The Journal of biological chemistry High 11572874
2004 HIF-1 directly activates Id2 transcription in hypoxic neuroblastoma cells via two functional HIF-1 binding sites at −725 and −1893 relative to the transcriptional start site, demonstrated by EMSA and ChIP; Id2 promoter-luciferase constructs are HIF-1-specifically activated in transfection assays. EMSA; chromatin immunoprecipitation (ChIP); luciferase reporter assay; actinomycin D transcription inhibition The Journal of biological chemistry High 15252039
2005 C/EBPβ directly activates Id2 transcription: nuclear translocation of C/EBPβ rapidly induces endogenous Id2; the most proximal of three C/EBPβ-binding elements in the 2.3 kb Id2 promoter is required for transactivation; EMSA identifies this as a C/EBPβ core-binding sequence; ChIP confirms C/EBPβ occupancy at the Id2 promoter in vivo; Id2 expression is reduced in C/EBPβ-deficient mammary glands. Inducible C/EBPβ-ERT nuclear translocation; reporter assay; EMSA; ChIP; Northern blot in C/EBPβ-null mammary glands Nucleic acids research High 15809228
2010 BMP6 activates Id2 transcription through Smad-binding elements (two GGCGCC palindromes and one GTCT element) in the Id2 promoter; gel shift and ChIP assays confirm physical Smad binding; mutation of these elements abolishes BMP responsiveness; a novel bipartite CGCC sequence contributes to Smad target recognition. Reporter assay; gel-shift (EMSA); ChIP; site-directed mutagenesis; BMP receptor inhibitor Biochemical and biophysical research communications High 20674548
2003 TGF-β represses Id2 expression in epithelial cells via induction of Mad2 and Mad4, which replace Myc-Max complexes with Mad-Max complexes on the Id2 promoter, providing a mechanism for TGF-β cytostatic program independent of c-Myc downregulation. Reporter assay; ChIP showing Myc-Max to Mad-Max promoter switching; Western blot; quantitative expression analysis across multiple epithelial cell lines The Journal of biological chemistry High 12824180
2006 Id2 acts as a master regulator of VEGF expression in pituitary tumor cells and neuroblastoma; in Rb+/− pituitary tumors, Id2-null cells show premature bHLH activation and p27Kip1 upregulation that impairs melanotrope proliferation and tumor initiation; N-Myc-driven Id2 expression is sufficient and necessary for VEGF expression in neuroblastoma. Id2-null/Rb+/− compound genetic mouse model; immunohistochemistry; gene expression analysis; neuroblastoma cell manipulation Molecular and cellular biology High 15831462
2008 Id2 regulates erythroid development by interacting with transcription factor PU.1 and modulating PU.1 and GATA-1 activities; Id2-null mice have expanded B-cell compartments, and Id2 acts as physiologically relevant inhibitor of E2A during B lymphopoiesis through direct antagonism. Id2 knockout mouse analysis; retroviral transduction/overexpression; shRNA knockdown; co-immunoprecipitation of Id2 with PU.1 Blood Medium 18523151
2010 Id2 promotes tumor cell migration and invasion through transcriptional repression of Semaphorin 3F (SEMA3F): E47 directly activates SEMA3F via two E-box sites in its promoter; Id2 acts as a dominant-negative inhibitor of E47, abrogating SEMA3F expression and its biological activities (F-actin depolymerisation, RhoA inactivation, migration inhibition). Reporter assay with E-box mutagenesis; SEMA3F knockdown rescue; migration/invasion assays; F-actin and RhoA activity assays Cancer research High 20388805
2011 p53 directly represses Id2 transcription by binding a conserved site within the Id2 promoter; p53-null neural progenitor cells have elevated Id2 and increased proliferation/self-renewal; suppression of Id2 is sufficient to restore normal proliferation to p53-null NPCs; elevated Id2 expression phenocopies p53 loss. Chromatin immunoprecipitation; Id2 KD by RNAi; p53-null mouse NPC analysis; promoter binding assay Stem cells (Dayton, Ohio) High 21608079
2014 The ubiquitin ligase ASB4 ubiquitinates and targets Id2 for proteasomal degradation in trophoblast/placental cells, promoting vascular differentiation; a degradation-resistant Id2 mutant co-expressed with ASB4 inhibits differentiation and functional vascular responses; Asb4-null placentas retain Id2 expression and show immature vascular patterning. Ubiquitination assay; proteasome inhibitor experiments; degradation-resistant mutant co-transfection; endothelial co-culture assays; Asb4-null mouse placenta analysis PloS one High 24586788
2016 Id2 represses multiple E-protein target genes including Socs3 in NK cells; Id2 deletion in mature NK cells leads to impaired IL-15 receptor signaling and metabolic dysfunction, rescued by strong IL-15 stimulation or genetic Socs3 deletion, demonstrating that Id2 regulates NK cell homeostasis by titrating E-protein activity at Socs3 and other target loci. Id2 conditional KO in mature NK cells; genetic Socs3/Id2 double-KO epistasis; IL-15 receptor signaling assays; metabolic function assays Immunity High 26795246
2016 Bcl6 binds the Id2 locus to repress Id2 expression in TFH cells; TH1 cells express higher Id2 than TFH cells; Id2 deficiency increases TFH frequency in an E-protein-dependent manner and blocks TH1 differentiation; Id2 reinforces TH1 differentiation by repressing E2A-dependent TFH-promoting programs. Id2 RNAi in T cells; T cell-specific Id2 KO mouse; ChIP (Bcl6 occupancy at Id2 locus); T cell subset phenotyping during viral infection Nature immunology High 27213691
2016 PDGF signaling upregulates USP1 via E2F transcription factors; USP1 stabilises ID2 protein; genetic ablation of Id2 delays glioma-induced mortality; pharmacologic USP1 inhibition reduces ID2 levels and delays tumorigenesis in a mouse proneural glioma model, establishing a PDGF–E2F–USP1–ID2 survival signalling cascade. E2F ChIP at Usp1 promoter; Id2 genetic KO in glioma model; USP1 pharmacologic inhibition; comparative transcriptomics Cancer research High 26951930
2018 Id2 mediates Treg-to-TH17 plasticity by sequestering the transcription activator E2A; expression of Id2 in iTreg cells reduces Foxp3 expression and induces TH17-related cytokines; Treg-specific Id2 overexpression in mice reduces the Treg compartment and causes immune dysregulation. Id2 overexpression in iTreg cells; Treg-specific Id2 transgenic mice; cellular fate-mapping; cytokine profiling Nature communications High 30413714
2020 Monoubiquitination of FANCD2 (within the FANCI–FANCD2/ID2 complex) promotes a large-scale conformational change that increases the complex's affinity for double-stranded DNA and enables it to encircle DNA by forming a secondary 'Arm' interface; monoubiquitination of FANCI protects the ubiquitin on FANCD2 from deubiquitination by USP1–UAF1, with key hydrophobic residues of FANCI's ubiquitin mediating this protection. Structural and biochemical analysis of ubiquitinated ID2 complex; DNA-binding affinity assays; deubiquitination protection assays with USP1–UAF1 EMBO reports High 32510829
2024 Id2 epigenetically regulates CD8+ T-cell exhaustion by binding, via its HLH domain, to Tcf3 (TCF1) and disrupting the Tcf3–Tal1 complex, thereby preventing Tcf3 from recruiting LSD1 histone demethylase to the Slamf6 promoter; this results in increased permissive H3K4me2 marks and greater chromatin accessibility at the Slamf6 promoter, promoting generation of Slamf6+ progenitor exhausted T cells. LSD1 inhibitor GSK2879552 rescues Id2-KO phenotype in tumour-bearing mice. Co-immunoprecipitation (HLH domain); ChIP for H3K4me2 and chromatin accessibility at Slamf6 promoter; Id2-KO mouse tumour model; LSD1 pharmacologic inhibition rescue Cellular & molecular immunology High 38287103
2021 ID2 in NK cells suppresses TCF1 amplitude during maturation; elevated TCF1 in ID2-deficient NK cells arrests their maturation and limits cytokine-induced IFN-γ production and anti-metastatic function, establishing ID2 as a transcriptional brake on TCF1 that controls the balance between immature expansion and terminal NK cell differentiation. Id2 conditional KO in NK cells; TCF1 reporter and protein level analysis; in vivo melanoma clearance assay; cytokine stimulation assays The Journal of experimental medicine High 33857289
2005 Ovol1 represses Id2 transcription in pachytene spermatocytes; Ovol1-deficient germ cells upregulate Id2 and fail to progress through the pachytene stage; Ovol1 represses the Id2 promoter in reporter assays, establishing Id2 as a direct transcriptional target of Ovol1 in male meiosis. Ovol1-KO mouse analysis; transcriptional profiling; Northern blot; Id2 promoter reporter assay Development (Cambridge, England) Medium 15716349
2009 Ebf1 down-regulates Id2 and Id3 expression in prepro-B cells to specify B-cell fate; enforced Ebf1 expression in IL-7Rα−/− bone marrow cells potently reduces Id2 and Id3 mRNA and restores B-cell differentiation in vivo; overexpression of either Id2 or Id3 blocks B-cell specification at the prepro-B stage. Retroviral Ebf1 expression in IL-7Rα-null bone marrow; Id2/Id3 overexpression in wild-type bone marrow; qRT-PCR; in vivo reconstitution Proceedings of the National Academy of Sciences of the United States of America High 19122139
2010 AMPK (PRKAA1/2) mediates stress-induced proteasome-dependent loss of ID2 protein in trophoblast stem cells at high stress levels, triggering differentiation; at low stress levels AMPK mediates metabolic adaptation without ID2 loss, establishing a dose-dependent AMPK–ID2 axis linking cellular stress to TSC differentiation. AMPK inhibitor/activator pharmacology; proteasome inhibitor experiments; PRKAA1/2 activation assays; immunoblot for ID2 in stressed TSCs Reproduction (Cambridge, England) Medium 20876741
2007 Id2 controls intestinal stem cell specification by restricting Wnt signalling activity at early embryonic stages; Id2-deficient intestinal epithelial cells precociously activate Wnt target genes and generate an expanded Lgr5+ progenitor pool. Id2-KO mouse; cell fate mapping; ex vivo organoid culture with Wnt target gene analysis; transcriptional profiling of adult Id2-null ISCs The EMBO journal Medium 28077488
2002 Id2 inhibits BETA2/NeuroD-mediated E-box-dependent gene expression in a dose-dependent manner by forming heterodimers that block BETA2/NeuroD binding to its target E-box sequence, as shown by EMSA; Id2 inhibits BETA2/NeuroD transcriptional activation in both HIT and HeLa cells. Yeast two-hybrid (interaction screen); EMSA; co-expression transcriptional reporter assays in HIT and HeLa cells Experimental & molecular medicine Medium 12526101
2013 Id2 restrains CD8+ T-cell memory differentiation by inhibiting E2A-mediated direct activation of Tcf7 (TCF1); Id2-deficient CD8+ T cells fail to upregulate Tbx21 for short-lived effector generation and instead adopt a memory fate with elevated Eomesodermin and Tcf7. Id2-KO CD8+ T-cell analysis during infection; E2A binding site reporter assay; gene expression profiling Journal of immunology (Baltimore, Md. : 1950) High 23536629
2006 BMP4 induces Id2 expression in AR42J pancreatic epithelial cells, and BMP4 stimulation promotes Id2 binding to NeuroD (a bHLH differentiation factor), thereby blocking endocrine differentiation and promoting expansion of pancreatic progenitors. BMP4 stimulation assays; co-immunoprecipitation of Id2–NeuroD; BMP4 neutralisation in mouse islet regeneration model; proliferation assays The Journal of biological chemistry Medium 16547003
2021 TGF-β signalling suppresses Id2 expression to decelerate cell-cycle in developing airway basal stem cells; reduced TGF-β signalling in adult tissue regeneration restores Id2 expression and initiates proliferation; persistent Id2 expression (via Id2 OE or Tgfbr2 KO) drives basal cell hyperplasia resembling a precancerous state, establishing the TGF-β–Id2 axis as a proliferation switch in airway basal cells. Id2 overexpression; Tgfbr2 conditional KO; single-cell transcriptomics; genetic validation in murine airway development and regeneration models Developmental cell High 34129836
2023 METTL3-mediated m6A modification stabilises ID2 mRNA in an m6A-YTHDF2-dependent manner in pancreatic cancer cells; METTL3 knockdown reduces m6A on ID2 mRNA and destabilises it; ID2 in turn controls stemness molecules NANOG and SOX2 via the PI3K–AKT pathway. METTL3 knockdown; m6A-seq/MeRIP; mRNA stability assay; YTHDF2 co-immunoprecipitation; PI3K–AKT pathway inhibition Cancer letters Medium 37196908
2019 Mtg16 represses Id2 transcription in dendritic cell progenitors; genome-wide DNA-binding analysis identifies Id2 as a direct Mtg16 target; Mtg16-deficient pDCs and cDC progenitors show aberrant Id2 induction; genetic deletion of Id2 partially rescues impaired pDC development in Mtg16-null mice. Mtg16-KO mouse; genome-wide ChIP-seq (DNA-binding analysis); Id2-KO rescue epistasis; flow cytometric DC subset analysis The Journal of experimental medicine High 24980046
2019 An Nfil3–Zeb2–Id2 genetic circuit controls cDC1 development: Nfil3 is required for the transition from Zeb2hi/Id2lo CDPs to Zeb2lo/Id2hi CDPs (earliest committed cDC1 progenitors); genetic epistasis shows this circuit blocks E-protein activity to exclude pDC potential and explains the switch in Irf8 enhancer usage. Single-cell RNA sequencing of CDPs; genetic epistasis (Nfil3 KO, Zeb2 KO, Id2 KO); DC progenitor phenotyping Nature immunology High 31406377
1995 bHLH transcription factors ME1, ME2, and NSCL1 stimulate Id2 promoter activity through E-box clusters in the 5′ regulatory region; co-expression of Id2 blocks this stimulatory effect, revealing a negative feedback loop in Id2 transcriptional regulation. Reporter/luciferase promoter assay; co-expression in F9 cells; retinoic acid differentiation assay FEBS letters Medium 7589553
1995 Id1 and Id2 can be phosphorylated in vitro by cAMP-dependent protein kinase; Id2 and Id3 can be phosphorylated by cdc2 kinase; all three (Id1, Id2, Id3) by PKC; however, phosphorylation by cAMP-kinase or PKC did not affect Id2/E47 dimerisation or DNA-binding inhibition in gel-shift assays. In vitro kinase assay; immunoprecipitation of phosphorylated Id1 from NGF-stimulated PC12 cells; gel-shift assay Biochemical and biophysical research communications Medium 7864897
2022 Under anchorage-independent conditions, E-cadherin loss de-represses Id2 transcription via a p120-catenin/Kaiso-dependent mechanism at a canonical Kaiso-binding sequence (TCCTGCNA) in the Id2 promoter; Id2 then accumulates in the cytosol and induces CDK4/6-dependent G0/G1 arrest through interaction with hypo-phosphorylated Rb, promoting anoikis resistance and lung colonisation in ILC models. Loss-of-function experiments; inducible E-cadherin restoration; promoter analysis; ChIP for Kaiso; co-immunoprecipitation of Id2 with Rb; subcellular fractionation; in vivo lung colonisation assay Oncogene High 35437308

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Id proteins Id1 and Id2 selectively inhibit DNA binding by one class of helix-loop-helix proteins. Molecular and cellular biology 567 1922066
2000 Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins. Nature 421 11034201
2003 Transcriptional profiling identifies Id2 function in dendritic cell development. Nature immunology 403 12598895
2011 The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets. Nature immunology 347 22057289
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
2006 Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth. Nature 227 16810178
2007 A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development. Cell 222 17604724
1996 Id2 specifically alters regulation of the cell cycle by tumor suppressor proteins. Molecular and cellular biology 215 8649364
2006 Transcriptional regulator Id2 mediates CD8+ T cell immunity. Nature immunology 203 17086188
2012 Notch, Id2, and RORγt sequentially orchestrate the fetal development of lymphoid tissue inducer cells. The Journal of experimental medicine 198 22430492
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
2005 Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor Id2. Nature cell biology 163 16311606
2001 Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2. Proceedings of the National Academy of Sciences of the United States of America 133 11296270
2013 Upregulated H19 contributes to bladder cancer cell proliferation by regulating ID2 expression. The FEBS journal 128 23399020
2019 An Id2RFP-Reporter Mouse Redefines Innate Lymphoid Cell Precursor Potentials. Immunity 127 30926235
2001 Id2 is a target of the beta-catenin/T cell factor pathway in colon carcinoma. The Journal of biological chemistry 124 11572874
2014 Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease. Nature immunology 118 24973820
2002 Id2 is critical for cellular proliferation and is the oncogenic effector of N-myc in human neuroblastoma. Cancer research 117 11782392
2004 Induction of ID2 expression by hypoxia-inducible factor-1: a role in dedifferentiation of hypoxic neuroblastoma cells. The Journal of biological chemistry 115 15252039
1997 Cdk2-dependent phosphorylation of Id2 modulates activity of E2A-related transcription factors. The EMBO journal 114 9029153
1999 Overexpression of the Helix-Loop-Helix protein Id2 blocks T cell development at multiple stages. Molecular immunology 113 10475604
2016 The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15. Immunity 103 26795246
2004 Id-1 and Id-2 proteins as molecular markers for human prostate cancer progression. Clinical cancer research : an official journal of the American Association for Cancer Research 99 15041724
1993 Neuronal expression of regulatory helix-loop-helix factor Id2 gene in mouse. Developmental biology 99 8224536
2005 Id2 mediates tumor initiation, proliferation, and angiogenesis in Rb mutant mice. Molecular and cellular biology 96 15831462
2019 An Nfil3-Zeb2-Id2 pathway imposes Irf8 enhancer switching during cDC1 development. Nature immunology 95 31406377
2016 Id2 reinforces TH1 differentiation and inhibits E2A to repress TFH differentiation. Nature immunology 95 27213691
2006 BMP4 regulates pancreatic progenitor cell expansion through Id2. The Journal of biological chemistry 92 16547003
2003 Upregulation of Id2, an oncogenic helix-loop-helix protein, is mediated by the chimeric EWS/ets protein in Ewing sarcoma. Oncogene 92 12527902
1998 The helix-loop-helix protein Id2 is overexpressed in human pancreatic cancer. Cancer research 87 9731481
2003 Denervation stimulates apoptosis but not Id2 expression in hindlimb muscles of aged rats. The journals of gerontology. Series A, Biological sciences and medical sciences 82 12902526
2013 Id2-mediated inhibition of E2A represses memory CD8+ T cell differentiation. Journal of immunology (Baltimore, Md. : 1950) 80 23536629
2014 Regulation of ACVR1 and ID2 by cell-secreted exosomes during follicle maturation in the mare. Reproductive biology and endocrinology : RB&E 78 24884710
2003 Mad upregulation and Id2 repression accompany transforming growth factor (TGF)-beta-mediated epithelial cell growth suppression. The Journal of biological chemistry 76 12824180
2010 Id2 promotes tumor cell migration and invasion through transcriptional repression of semaphorin 3F. Cancer research 72 20388805
2006 E Proteins and Id2 converge on p57Kip2 to regulate cell cycle in neural cells. Molecular and cellular biology 70 16705184
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
2006 The protein ENH is a cytoplasmic sequestration factor for Id2 in normal and tumor cells from the nervous system. Proceedings of the National Academy of Sciences of the United States of America 67 16549780
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
2021 Sleep down state-active ID2/Nkx2.1 interneurons in the neocortex. Nature neuroscience 62 33619404
2003 TH2 dominance and defective development of a CD8+ dendritic cell subset in Id2-deficient mice. The Journal of allergy and clinical immunology 61 12532109
2019 LncRNA ID2-AS1 suppresses tumor metastasis by activating the HDAC8/ID2 pathway in hepatocellular carcinoma. Cancer letters 60 31730902
2018 Inflammation-induced Id2 promotes plasticity in regulatory T cells. Nature communications 60 30413714
2008 Id2 intrinsically regulates lymphoid and erythroid development via interaction with different target proteins. Blood 58 18523151
2004 Degradation of the Id2 developmental regulator: targeting via N-terminal ubiquitination. Biochemical and biophysical research communications 58 14733935
2019 Blocking lncRNA H19-miR-19a-Id2 axis attenuates hypoxia/ischemia induced neuronal injury. Aging 57 31170091
2023 METTL3 promotes pancreatic cancer proliferation and stemness by increasing stability of ID2 mRNA in a m6A-dependent manner. Cancer letters 56 37196908
2005 Ovol1 regulates meiotic pachytene progression during spermatogenesis by repressing Id2 expression. Development (Cambridge, England) 56 15716349
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
2004 Id2 drives differentiation and suppresses tumor formation in the intestinal epithelium. Cancer research 53 15492237
2005 Differential involvement of PU.1 and Id2 downstream of TGF-beta1 during Langerhans-cell commitment. Blood 51 16223775
2018 Transcription factor ID2 prevents E proteins from enforcing a naïve T lymphocyte gene program during NK cell development. Science immunology 50 29703840
2017 LncRNA H19 regulates ID2 expression through competitive binding to hsa-miR-19a/b in acute myelocytic leukemia. Molecular medicine reports 50 28765931
2010 Identification of BMP-responsive elements in the mouse Id2 gene. Biochemical and biophysical research communications 50 20674548
2002 Id2 negatively regulates B cell differentiation in the spleen. Journal of immunology (Baltimore, Md. : 1950) 47 12023345
2017 Id2 controls specification of Lgr5+ intestinal stem cell progenitors during gut development. The EMBO journal 46 28077488
2014 ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2. The Journal of experimental medicine 46 24980046
2013 Id2 influences differentiation of killer cell lectin-like receptor G1(hi) short-lived CD8+ effector T cells. Journal of immunology (Baltimore, Md. : 1950) 41 23325888
2005 Hindlimb unloading increases muscle content of cytosolic but not nuclear Id2 and p53 proteins in young adult and aged rats. Journal of applied physiology (Bethesda, Md. : 1985) 41 16282427
2014 The ubiquitin ligase ASB4 promotes trophoblast differentiation through the degradation of ID2. PloS one 40 24586788
2010 Cellular stress causes reversible, PRKAA1/2-, and proteasome-dependent ID2 protein loss in trophoblast stem cells. Reproduction (Cambridge, England) 39 20876741
2011 The small molecule harmine regulates NFATc1 and Id2 expression in osteoclast progenitor cells. Bone 38 21504804
2020 Differential functions of FANCI and FANCD2 ubiquitination stabilize ID2 complex on DNA. EMBO reports 37 32510829
2011 p53 directly represses Id2 to inhibit the proliferation of neural progenitor cells. Stem cells (Dayton, Ohio) 37 21608079
2009 TGF-beta repression of Id2 induces apoptosis in gut epithelial cells. Oncogene 37 19137015
2005 ID1 and ID2 are retinoic acid responsive genes and induce a G0/G1 accumulation in acute promyelocytic leukemia cells. Leukemia 37 15744343
2021 Airway basal stem cells reutilize the embryonic proliferation regulator, Tgfβ-Id2 axis, for tissue regeneration. Developmental cell 36 34129836
2008 Therapeutic targeting of Id2 reduces growth of human colorectal carcinoma in the murine liver. Oncogene 36 18806828
2013 Demyelination initiated by oligodendrocyte apoptosis through enhancing endoplasmic reticulum-mitochondria interactions and Id2 expression after compressed spinal cord injury in rats. CNS neuroscience & therapeutics 35 23937638
2010 Polycomb repressor complex 2 regulates HOXA9 and HOXA10, activating ID2 in NK/T-cell lines. Molecular cancer 35 20565746
2015 Snail interacts with Id2 in the regulation of TNF-α-induced cancer cell invasion and migration in OSCC. American journal of cancer research 34 26175937
2013 Stress induces AMPK-dependent loss of potency factors Id2 and Cdx2 in early embryos and stem cells [corrected]. Stem cells and development 33 23316940
2010 Benzo(a)pyrene causes PRKAA1/2-dependent ID2 loss in trophoblast stem cells. Molecular reproduction and development 31 20422711
2005 Regulation of Id2 expression by CCAAT/enhancer binding protein beta. Nucleic acids research 31 15809228
2016 PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-Mediated Survival of Proneural Glioma Cells. Cancer research 30 26951930
2016 Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia. Cancer cell 30 27374225
2013 Batf3 and Id2 have a synergistic effect on Irf8-directed classical CD8α+ dendritic cell development. Journal of immunology (Baltimore, Md. : 1950) 30 24227775
2012 Transcriptional regulator Id2 is required for the CD4 T cell immune response in the development of experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md. : 1950) 30 22745378
2024 Id2 epigenetically controls CD8+ T-cell exhaustion by disrupting the assembly of the Tcf3-LSD1 complex. Cellular & molecular immunology 29 38287103
2002 Inhibition of BETA2/NeuroD by Id2. Experimental & molecular medicine 29 12526101
2022 ASCL1 phosphorylation and ID2 upregulation are roadblocks to glioblastoma stem cell differentiation. Scientific reports 28 35149717
2015 TNFα signaling regulates cystic epithelial cell proliferation through Akt/mTOR and ERK/MAPK/Cdk2 mediated Id2 signaling. PloS one 28 26110849
2014 The Fanconi anemia ID2 complex: dueling saxes at the crossroads. Cell cycle (Georgetown, Tex.) 28 25486561
2021 The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude. The Journal of experimental medicine 27 33857289
2019 The Transcriptional Regulator Id2 Is Critical for Adipose-Resident Regulatory T Cell Differentiation, Survival, and Function. Journal of immunology (Baltimore, Md. : 1950) 27 31201238
2017 BMP4 enhances hepatocellular carcinoma proliferation by promoting cell cycle progression via ID2/CDKN1B signaling. Molecular carcinogenesis 27 28543546
2014 Id2 mediates oligodendrocyte precursor cell maturation arrest and is tumorigenic in a PDGF-rich microenvironment. Cancer research 27 24425046
2023 Progesterone attenuates Th17-cell pathogenicity in autoimmune uveitis via Id2/Pim1 axis. Journal of neuroinflammation 26 37344856
2022 The CDK1/TFCP2L1/ID2 cascade offers a novel combination therapy strategy in a preclinical model of bladder cancer. Experimental & molecular medicine 26 35729325
2014 Id2 represses E2A-mediated activation of IL-10 expression in T cells. Blood 26 24723679
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) 26 24379125
2009 The intracellular localization of ID2 expression has a predictive value in non small cell lung cancer. PloS one 26 19129913
1995 Helix-loop-helix transcription factors regulate Id2 gene promoter activity. FEBS letters 26 7589553
2021 ID2 Inhibits Bladder Cancer Progression and Metastasis via PI3K/AKT Signaling Pathway. Frontiers in cell and developmental biology 25 34746132
2009 ID2 (inhibitor of DNA binding 2) is a rhythmically expressed transcriptional repressor required for circadian clock output in mouse liver. The Journal of biological chemistry 25 19740747
2007 Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes. Oncogene 25 17310985
1995 Expression of Id2 and Id3 mRNA in human lymphocytes. Leukemia research 25 8632670
2022 Loss of E-cadherin leads to Id2-dependent inhibition of cell cycle progression in metastatic lobular breast cancer. Oncogene 24 35437308
1995 Phosphorylation of helix-loop-helix proteins ID1, ID2 and ID3. Biochemical and biophysical research communications 24 7864897
2023 Quercetin prevents the ferroptosis of OPCs by inhibiting the Id2/transferrin pathway. Chemico-biological interactions 23 37230155