| 1994 |
Constitutive expression of Id1 in transgenic mice impairs B cell development at an early stage, reducing V(D)J recombination and expression of immunoglobulin, RAG-1, RAG-2, and lambda 5 genes, demonstrating that Id1 (as a dominant-negative inhibitor of bHLH transcription factors) blocks B lymphocyte differentiation. |
Transgenic mouse model with constitutive Id1 expression; B cell phenotyping by flow cytometry and PCR |
Cell |
High |
8001126
|
| 1995 |
Id-1 suppresses mammary epithelial cell differentiation: stable Id-1 overexpression prevents beta-casein expression in response to differentiation signals and causes invasion of the basement membrane, while Id-1 antisense expression stabilizes differentiation, establishing Id-1 as an inhibitor of bHLH-driven mammary differentiation. |
Stable transfection of Id-1 expression and antisense vectors in SCp2 mammary epithelial cells; beta-casein expression, 3D culture morphology, and growth assays |
Molecular and cellular biology |
High |
7760836
|
| 1999 |
Targeted disruption of Id1 and Id3 in mice causes premature neuroblast withdrawal from the cell cycle, expression of neural differentiation markers, vascular malformations in the forebrain, and failure of tumor xenograft angiogenesis, establishing Id1 as required for timing of neuronal differentiation and vascular invasiveness. |
Id1/Id3 double-knockout mice; tumor xenograft implantation; histological and immunological analysis of neurogenesis and angiogenesis |
Nature |
High |
10537105
|
| 2002 |
Id1 transcriptionally represses thrombospondin-1 (TSP-1): Id1-null mouse embryo fibroblasts secrete elevated TSP-1 that inhibits endothelial cell migration, and in vivo neovascularization defects in Id1-null mice are rescued by a TSP-1 neutralizing antibody, identifying TSP-1 as a major downstream effector through which Id1 promotes angiogenesis. |
PCR-select subtractive hybridization on wild-type vs. Id1 knockout MEFs; endothelial migration assay with TSP-1 depletion; in vivo Matrigel neovascularization assay with TSP-1 neutralizing antibody |
Cancer cell |
High |
12498716
|
| 2003 |
Id-1 promotes cell survival in prostate cancer cells via activation of the NF-κB signaling pathway: ectopic Id-1 increases nuclear translocation of p65/p50, upregulates Bcl-xL and ICAM-1, inactivates Bax and caspase 3, conferring resistance to TNFα-induced apoptosis; antisense Id-1 reduces nuclear p65/p50 and sensitizes cells to apoptosis. |
Stable Id-1 transfection in LNCaP cells; NF-κB reporter assays; Western blot for p65/p50 nuclear translocation; apoptosis assays; antisense knockdown in DU145 cells |
Oncogene |
High |
12881706
|
| 2004 |
BMP-2 increases Id1 expression, which in turn destabilizes Mash1 protein by shifting the E47/Id1 ratio: elevated Id1 promotes proteasomal degradation of Mash1, whereas E47 stabilizes Mash1; the E47/Id1 ratio also regulates CK2-mediated phosphorylation of Mash1 on Ser152, modulating Mash1-E47 heterodimer interaction. |
BMP-2 treatment of neuroendocrine lung carcinoma cells; Id1 overexpression and knockout; E47 overexpression; pulse-chase protein stability assays; phosphorylation analysis |
The EMBO journal |
High |
15318167
|
| 2004 |
Id1 is a downstream effector of the p53-dependent DNA damage response: DNA damage represses ID1 expression in a p53-dependent manner via the p53 target DEC1, which inhibits ID1 promoter activity; overexpression of ID1 promotes cell proliferation through inhibition of p21 and substantially decreases DNA damage-induced premature senescence. |
DNA damage treatment of cells; siRNA knockdown of DEC1; ID1 promoter deletion/mutation assays; ID1 overexpression with proliferation and senescence assays |
The Journal of biological chemistry |
High |
18556654
|
| 2004 |
E12 and E47 physically interact with Id1 to stabilize it: cotransfection of E12 or E47 with Id1 markedly reduces Id1 degradation rate (t1/2 from ~1 h to ~8 h) and alters its subcellular localization, demonstrating that E-protein heterodimerization regulates Id1 protein stability via the ubiquitin-proteasome system. |
Co-transfection of E12/E47 with Id1 in non-muscle cells; pulse-chase degradation assays; NLS-mutant subcellular localization analysis; proteasome inhibitor experiments |
Oncogene |
High |
16007194
|
| 2004 |
Ubiquitin-dependent degradation of Id1 and Id3 is mediated by the COP9 signalosome (CSN): Id1/Id3 (but not Id2/Id4) bind CSN subunit CSN5 in mammalian two-hybrid assays; Id3 physically interacts with the CSN complex and CSN5/CSN7; curcumin and emodin (CSN-associated kinase inhibitors) stimulate Id1/Id3 ubiquitination and proteasomal degradation; overexpression of CSN2 stabilizes Id3 protein. |
Mammalian two-hybrid analysis; pull-down and far-Western experiments; transfection with His-ubiquitin and Id3; pharmacological treatment with curcumin/emodin; CSN2 overexpression |
Journal of molecular biology |
High |
15451666
|
| 2007 |
Id1 protein undergoes PKA-regulated nucleocytoplasmic shuttling in endothelial cells: Id1 is nuclear in HUVECs on uncoated plates but translocates to the cytoplasm during capillary-like structure formation on Matrigel via CRM1/exportin-dependent nuclear export; PKA activation inhibits this export (Ser-5 phosphorylation implicated), suggesting nuclear Id1 function is controlled by localization during angiogenesis. |
Live imaging of GFP-Id1 in HUVECs; leptomycin B treatment (CRM1 inhibitor); PKA activators (dbcAMP, forskolin) and inhibitors (H-89); Ser-5 mutagenesis of Id1 |
The Journal of biological chemistry |
High |
17412691
|
| 2007 |
Id1 promotes the generation of endothelial progenitor cells (EPCs) in bone marrow by restraining expression of p21: Id1 knockout mice lack circulating EPCs and show increased p21 expression; genetic ablation of p21 in Id1-null mice rescues the EPC population, restores BM-derived angiogenesis, and normalizes tumor growth. |
Genetically modified mouse models (Id1-KO, p21-KO, Id1/p21 double-KO); flow cytometry for EPCs; tumor growth assays |
PloS one |
High |
18092003
|
| 2007 |
Id1, but not Id3, is expressed in long-term repopulating hematopoietic stem cells (LT-HSCs) and is required for their maintenance: Id1-GFP knock-in marks LT-HSCs; Id1-deficient (but not Id3-deficient) bone marrow shows impaired engraftment in secondary transplantation assays, demonstrating a unique role for Id1 in LT-HSC self-renewal. |
Id1-GFP knock-in mouse model; serial bone marrow transplantation; flow cytometry for HSC populations |
Blood |
High |
17622570
|
| 2007 |
Id1 overexpression inhibits BMP signaling by inducing Twist-1 degradation: Twist-1 inhibits BMP signaling by forming a complex with Smad4 and HDAC1; Id1 promotes Twist-1 degradation and thereby de-represses BMP target gene expression, establishing Id1 as a positive regulator of BMP signaling through a feedback loop. |
Co-immunoprecipitation in MC3T3-E1 cells; osteoblast differentiation assays; HDAC inhibitor (trichostatin) treatment; Id1 overexpression and Twist-1 stability assays |
Journal of cell science |
Medium |
17374642
|
| 2008 |
COX-2-derived PGE2 activates Id-1 transcription via the EP4 receptor → EGFR → ERK1/2 → Egr-1 pathway: PGE2 induces amphiregulin release to transactivate EGFR, leading to Egr-1 binding to the Id-1 promoter; this cascade increases Id-1 expression and mammary epithelial cell invasiveness. |
EP4 agonist treatment; EGFR/ERK inhibitor experiments; chromatin immunoprecipitation for Egr-1 at the Id-1 promoter; COX-2 siRNA silencing; cell migration/invasion assays |
The Journal of biological chemistry |
High |
18842581
|
| 2008 |
Id-1 activates the Akt pathway by inhibiting PTEN transcription through downregulation of p53: Id-1 reduces p53 binding to the PTEN promoter (confirmed by ChIP and serial promoter deletion); this activates Akt→ canonical Wnt signaling, leading to GSK-3β phosphorylation, β-catenin nuclear localization, and p27(Kip1) cytoplasmic sequestration. |
Id-1 overexpression in MCF7 cells; promoter deletion assays and ChIP for p53 at PTEN promoter; Western blot for Akt/β-catenin/p27 phosphorylation; TCF/LEF reporter assay |
Oncogene |
High |
19079342
|
| 2009 |
ID1 is a transcriptional target of JAK2-STAT5 signaling in erythroid cells: STAT5 binds and transactivates a downstream enhancer of ID1 (confirmed by ChIP); ID1 promotes survival of primary erythroid cells; ID1 expression correlates with JAK2V617F mutation in erythroid cells and polycythemia vera patients. |
Comparative genomics and chromatin immunoprecipitation for STAT5 at ID1 enhancer; ID1 knockdown and overexpression in primary fetal liver erythroid differentiation assay |
Blood |
High |
19571317
|
| 2009 |
High expression of Id1 identifies a rare population of B1-type adult neural stem cells (GFAP+ astrocytes) in the subventricular zone; Id1-high cells self-renew asymmetrically generating progeny with progressively lower Id1; Id genes are necessary for self-renewal capacity, demonstrated by loss-of-function. |
Id1-GFP knock-in reporter mouse; FACS isolation of Id1-high cells; neurosphere and in vivo transplantation assays; Id gene knockout |
Cell stem cell |
High |
19896442
|
| 2009 |
Id1 has a non-cell-autonomous role in maintaining the hematopoietic progenitor cell niche: transplantation experiments show that Id1(-/-) microenvironment impairs normal hematopoietic development; Id1(-/-) stromal cells display altered cytokine production, demonstrating that Id1 regulates the niche rather than HSC intrinsic function. |
Reciprocal bone marrow transplantation between WT and Id1-KO mice; in vitro cytokine production assays of Id1-KO stromal cells |
Blood |
High |
19478045
|
| 2011 |
Smurf2 is the E3 ubiquitin ligase that ubiquitinates Id1 and Id3: Smurf2-mediated ubiquitination and degradation of Id1 regulates p16 expression during cellular senescence, establishing a mechanistic link between Smurf2, Id1, and p16 in senescence. |
Co-immunoprecipitation; ubiquitination assays; Smurf2 overexpression and knockdown; senescence assays; p16 expression analysis |
Aging cell |
High |
21933340
|
| 2013 |
Id1 promotes breast cancer metastasis by interacting with TFAP2A to suppress S100A9 expression: ID1-TFAP2A interaction suppresses S100A9, which in turn permits elevated RhoC expression; reestablishment of S100A9 rescues the migratory/invasive and in vivo metastatic phenotypes induced by Id1. |
Co-immunoprecipitation of Id1 with TFAP2A; S100A9 knockdown/overexpression rescue; in vitro migration/invasion assays; in vivo metastasis assay |
Molecular cancer research : MCR |
Medium |
24948111
|
| 2013 |
E47 and Id1 physically interact in mesenchymal breast carcinoma and MDCK-E47 EMT cells; ChIP demonstrates that E47 binds the endogenous E-cadherin promoter in a complex devoid of Id1; both E47 and Id1 are required to maintain the mesenchymal phenotype, operating through mechanisms independent of Id1 dominant-negative action on E-cadherin transcription. |
Co-immunoprecipitation of E47 and Id1; chromatin immunoprecipitation at E-cadherin promoter; Id1 knockdown in EMT cells |
PloS one |
Medium |
23555842
|
| 2013 |
p53 represses Id1 expression through BMP-Smad1-dependent and -independent mechanisms: p53 deficiency leads to elevated Smad1 and Id1 expression; Id1 upregulation contributes to both augmented NSC proliferation and accelerated neuronal differentiation in p53-null neural stem cells. |
p53-knockout neural stem cells; in vivo BrdU labeling; Smad1 siRNA; Id1 overexpression; differentiation assays |
Stem cells and development |
Medium |
23199293
|
| 2013 |
Serum induction of Id1 is mediated by a BMP-responsive element (BRE) in the Id1 promoter: BMP pathway inhibition (Smad4 siRNA, noggin, dorsomorphin) blocks serum induction of Id1; BMP2 alone is sufficient to induce Id1; the BRE is necessary and sufficient for serum responsiveness of Id1. |
Id1 promoter deletion/mapping in serum-stimulated fibroblasts; siRNA depletion of Smad4; BMP antagonist (noggin) and receptor inhibitor (dorsomorphin) treatment; BMP2 stimulation |
Biochimica et biophysica acta |
High |
23948603
|
| 2015 |
Id1 upregulation in response to tumour-derived TGFβ drives a switch from dendritic cell differentiation to myeloid-derived suppressor cell expansion: genetic inactivation of Id1 corrects the myeloid imbalance, and Id1 overexpression in the absence of tumour-derived factors re-creates immunosuppression and suppresses CD8 T-cell proliferation, identifying Id1 as a key mediator of tumour-induced immunosuppression. |
Id1 genetic inactivation and overexpression in mouse models; TGFβ stimulation; DC differentiation assays; CD8 T-cell proliferation assays |
Nature communications |
High |
25924227
|
| 2016 |
COX-2-derived PGE2 induces Id1 in GBM cells via the EP4 receptor → ERK1/2 MAPK → Egr1 transcription factor pathway; this induction of Id1 is required for optimal GBM cell self-renewal and radiation resistance, demonstrated by siRNA and pharmacological pathway inhibition combined with chromatin immunoprecipitation. |
dmPGE2 stimulation of mouse and human GBM cells; siRNA knockdown and small molecule inhibitors of EP4, ERK1/2, Egr1; ChIP for Egr1 at Id1 promoter; sphere formation and radiation resistance assays |
Neuro-oncology |
High |
27022132
|
| 2016 |
ID1 suppresses CULLIN3 ubiquitin ligase in glioblastoma stem cells (GSCs): ID1 promotes GSC proliferation, self-renewal, and tumorigenicity by suppressing CULLIN3, leading to accumulation of CYCLIN E and CULLIN3 substrates GLI2 and DVL2 (confirmed by proteomics showing CULLIN3-GLI2/DVL2 interaction and ubiquitination); combined pharmacological inhibition of GLI2 and β-CATENIN diminishes GSC properties. |
ID1 knockdown/overexpression in human GSCs; proteomics analysis of CULLIN3 interactome; ubiquitination assays for GLI2/DVL2; combinatorial pharmacological inhibition; in vivo tumorigenicity assays |
Cell reports |
High |
27477274
|
| 2016 |
ID1 promotes resistance to etoposide-induced apoptosis through a c-Jun/c-Fos (AP-1)-dependent mechanism: AP-1 binding sites in the ID1 promoter mediate ID1 upregulation upon etoposide treatment; ablation of c-Jun/c-Fos or ID1 enhances etoposide-mediated apoptosis via caspase 3 activation and PARP cleavage. |
AP-1 site mutagenesis in ID1 promoter; c-Jun/c-Fos and ID1 siRNA knockdown; caspase 3 activity and PARP cleavage assays in esophageal cancer cells |
The Journal of biological chemistry |
Medium |
26858249
|
| 2017 |
Id1 promotes obesity by suppressing brown adipose thermogenesis through two direct molecular interactions: (1) Id1 binds and suppresses PGC1α transcriptional activity to reduce UCP1 and thermogenic gene expression; (2) Id1 directly interacts with and suppresses Ebf2 transcriptional activity, reducing Prdm16 expression and brown/beige adipocyte fate determination. |
Adipose-specific Id1 transgenic mice; Id1-deficient mouse embryonic fibroblasts; co-immunoprecipitation of Id1 with PGC1α and Ebf2; chromatin/reporter assays; cold-exposure and HFD phenotype analysis |
Diabetes |
High |
28270523
|
| 2017 |
ID1 inhibits BMPR2 expression in glioblastoma stem cells through MYC-driven upregulation of miR-17 and miR-20a, thereby abrogating BMP differentiation signaling and promoting self-renewal; ID1 simultaneously activates WNT and SHH signaling by increasing MYC expression. |
ID1 overexpression and knockdown in GSCs; miRNA expression analysis; Western blotting for BMPR2; WNT/SHH inhibitor treatment; in vivo tumor survival assay |
Clinical cancer research |
Medium |
29208670
|
| 2017 |
ID1 confers oxaliplatin resistance in hepatocellular carcinoma by activating the pentose phosphate pathway (PPP): ID1 induces G6PD promoter transcription and activates PPP through Wnt/β-catenin/c-MYC signaling, increasing NADPH and reducing ROS; ID1 knockdown decreases G6PD expression, blocks PPP, elevates ROS, and induces apoptosis. |
lentiviral shRNA knockdown of ID1 in oxaliplatin-resistant HCC cells; G6PD promoter luciferase assay; NADPH/ROS measurement; β-catenin/c-MYC inhibitor experiments; in vivo xenograft |
Journal of experimental & clinical cancer research |
Medium |
29169374
|
| 2018 |
Hyaluronic acid–CD44 interactions promote BMP4/7-dependent Id1/3 expression: Co-IP demonstrates that CD44 physically associates with the BMP type II receptor ACVR2B; depletion of HA or CD44 reduces BMP4/7-driven Id1/3 expression; exogenous HA enhances it, linking pericellular matrix to Id1 regulation in melanoma. |
HA depletion by hyaluronidase and 4-MU; CD44 knockdown; exogenous HA treatment; Co-immunoprecipitation of CD44 with ACVR2B; Western blot for Id1/3 |
Scientific reports |
Medium |
30297743
|
| 2018 |
Id1 ablation protects hematopoietic stem cells from stress-induced exhaustion: cytokine induction of Id1 drives HSC proliferation, mitochondrial biogenesis, and ROS production; Id1-/- HSCs are quiescent, accumulate less DNA damage, and display a blunted proliferative response to γ-irradiation, genotoxic stress, and aging. |
Id1 genetic ablation; serial bone marrow transplantation; BrdU proliferation assay; ROS measurement; mitochondrial biogenesis assay; γ-irradiation model |
Cell stem cell |
High |
30082068
|
| 2019 |
ID1 expression is selected for in pancreatic ductal adenocarcinoma to escape TGFβ-induced tumor suppression: ID1 uncouples TGFβ-induced EMT from apoptosis by preventing the imbalance of SOX4 and KLF5 that normally triggers cell death; AKT signaling converges on ID1 to preserve its expression, and TGFβ-mediated repression of ID1 is evaded during PDA progression. |
Genetic loss-of-function and gain-of-function of ID1 in pancreatic progenitor cells; TGFβ treatment; apoptosis and EMT assays; analysis of PDA patient samples for ID1 genetic/epigenetic alterations; AKT inhibitor experiments |
Cancer discovery |
High |
31582374
|
| 2019 |
CRISPR-mediated knockout of ID1 in glioblastoma, breast adenocarcinoma, and melanoma cells dramatically reduces tumor progression through transcriptional downregulation of EGF, resulting in decreased EGFR phosphorylation; ID1-positive cells are enriched by temozolomide chemotherapy and drive tumor recurrence. |
CRISPR-Cas9 knockout of ID1 in three cancer cell lines; EGF/EGFR expression and phosphorylation analysis; in vivo tumor growth assays; temozolomide treatment and recurrence tracking |
Cancer research |
High |
31292163
|
| 2019 |
Salt-inducible kinase 1 (SIK1) negatively regulates Id1 expression in osteoblasts by phosphorylating CRTC1, preventing CRTC1 from enhancing CREB transcriptional activity at osteogenic genes including Id1; BMP2 suppresses SIK1 via PKA to permit Id1 expression and osteogenesis. |
SIK1 gene knockdown in primary preosteoblasts; SIK1-KO mice; CRTC1 phosphorylation assays; osteoblast differentiation and bone mineralization assays; BMP2/PKA pathway inhibitor experiments |
Cell death & disease |
Medium |
31672960
|
| 2020 |
ID1 confers cancer cell chemoresistance through a STAT3/ATF6-mediated induction of autophagy: ID1 activates NF-κB p65 nuclear translocation, which increases IL-6 secretion, activating STAT3 (Y705 phosphorylation), which transcriptionally upregulates ATF6 to induce ER stress-dependent autophagy and resistance to cisplatin/paclitaxel. |
ID1 overexpression/siRNA in ovarian cancer cells; luciferase assays for NF-κB and STAT3/ATF6 promoters; IL-6 ELISA; phosphorylation Western blot; autophagy assays; clinical correlation in 1104 HGSOC samples |
Cell death & disease |
High |
32080166
|
| 2020 |
Id1-/-Id3-/- sinusoidal endothelial cells (SECs) undergo increased apoptosis due to reduced Bcl2-family gene expression, and show increased p21/p27 expression and impaired proliferation; reduced E2-2 expression rescues proliferation, demonstrating that Id1/Id3 maintain BM SEC survival and regeneration by suppressing E-protein activity. |
Conditional Id1/Id3 deletion in adult ECs; SEC apoptosis assays; Bcl2 family gene expression; p21/p27 analysis; E2-2 knockdown rescue; irradiation survival model |
Cell reports |
High |
32348770
|
| 2020 |
BMP signaling controls id1 expression in neural stem cells through conserved Smad1/5 and Smad4 binding motifs in a cis-regulatory module (CRM): deletion mapping and mutation of these binding sites in stable transgenic zebrafish reveal that BMP-Smad signaling is required for id1 expression in radial glial NSCs under both homeostatic and regenerative neurogenesis. |
Systematic CRM deletion mapping in stable transgenic zebrafish; Smad binding site mutation; pharmacological BMP pathway inhibition; transcriptome analysis of injured/uninjured telencephala |
Stem cells |
High |
32246536
|
| 2021 |
rHDL-apoE3 promotes endothelial cell migration through ID1-mediated activation of ERK1/2 and AKT: siRNA silencing of ID1 markedly reduces rHDL-apoE3-triggered EC migration and inhibits phosphorylation of ERK1/2 and AKT, placing ID1 upstream of MEK1/2 and PI3K pathways in EC migration. |
siRNA-mediated ID1 knockdown in HCAEC and EA.hy926 cells; wound healing and transwell migration assays; Western blot for phospho-ERK1/2, AKT, eNOS, p38 MAPK; pathway inhibitors PD98059 and LY294002 |
Metabolism: clinical and experimental |
Medium |
34875308
|
| 2023 |
ID1 in tumor-associated macrophages (TAMs) interacts with STAT1 to promote its cytoplasmic distribution, inhibiting STAT1-mediated transcription of SerpinB2 and CCL4, two secretory factors that suppress cancer stemness and recruit CD8+ T cells; reducing ID1 in TAMs ameliorates CRC progression and improves immunotherapy sensitivity. |
Co-immunoprecipitation of ID1 with STAT1; STAT1 subcellular localization assays; SerpinB2/CCL4 promoter analysis; ID1 knockdown in TAMs; CD8+ T cell infiltration measurement; in vivo CRC tumor model |
Nature communications |
High |
37996458
|
| 2023 |
ID1 in bone marrow mesenchymal stem cells promotes AML progression through a non-cell-autonomous mechanism: ID1 interacts with RNF4 (E3 ubiquitin ligase), reducing SP1 ubiquitination; preserved SP1 drives Angptl7 expression in the microenvironment, which supports AML cell proliferation. |
ID1-interactome analysis by proteomics; Co-IP of ID1 with RNF4; SP1 ubiquitination assays; ID1 truncation to disrupt ID1-RNF4 interaction; AML co-culture and mouse model |
Blood |
High |
37319434
|
| 2005 |
CASK physically interacts with Id1: yeast two-hybrid screening identified Id1 as a novel CASK-interacting protein, confirmed by endogenous co-immunoprecipitation from ECV304 cells; mammalian two-hybrid assays show differential CASK binding to Id1 and its alternative splicing variant. |
Yeast two-hybrid screening; co-immunoprecipitation of endogenous CASK and Id1; mammalian two-hybrid interaction assays |
Biochemical and biophysical research communications |
Low |
15694377
|