| 2012 |
IGF2BP1 promotes tumor cell migration velocity by inhibiting translation of MAPK4 mRNA, which prevents MK5 activation and HSP27 phosphorylation, thereby reducing G-actin sequestration and increasing F-actin polymerization. Simultaneously, IGF2BP1 stabilizes PTEN mRNA, enhancing PTEN expression and antagonizing PIP3 signaling to enforce RAC1-dependent cell polarization and directionality. |
RNA binding assays, knockdown/overexpression in tumor cell lines, cell migration assays, epistasis with MK5, RAC1, and HSP27 |
Genes & development |
High |
22279049
|
| 2019 |
IGF2BP1 promotes SRF expression by impairing miRNA-directed decay of SRF mRNA in an m6A-dependent manner. IGF2BP1 associates with target mRNAs in RISC-free complexes and its deletion enhances mRNA association with AGO2, indicating IGF2BP1 antagonizes miRNA-mediated mRNA degradation by competing with RISC. |
Gene expression analysis, AGO2-RIP, miRNA depletion experiments, m6A-dependent assays, knockdown/overexpression in cancer cell lines and nude mouse xenografts |
Nucleic acids research |
High |
29660014 30371874
|
| 2020 |
The oncopeptide RBRP (encoded by LINC00266-1) directly binds IGF2BP1 and strengthens its m6A recognition on target RNAs such as c-Myc mRNA, increasing mRNA stability and c-Myc expression to promote tumorigenesis. |
Co-immunoprecipitation, RNA pulldown, m6A recognition assays, mRNA stability assays, overexpression/knockdown in cancer cells |
Nature communications |
Medium |
32245947
|
| 2021 |
IGF2BP1 recognizes m6A sites in the 3'UTR of PEG10 mRNA and recruits PABPC1 to enhance PEG10 mRNA stability, increasing PEG10 protein expression in endometrial cancer cells. |
RIP-seq, MeRIP-seq, RNA-seq, Co-immunoprecipitation and mass spectrometry to identify PABPC1 as interacting partner, mRNA stability assays |
Theranostics |
Medium |
33391523
|
| 2022 |
A small molecule cucurbitacin B (CuB) directly targets IGF2BP1 at Cys253 in the KH1-2 domains, causing an allosteric effect that blocks IGF2BP1 recognition of m6A mRNA targets such as c-MYC. |
Chemical genetics, direct binding assays (Cys253 targeting), KH domain mutagenesis, m6A RNA binding assays, in vivo xenograft models |
ACS central science |
Medium |
36032766
|
| 2023 |
PRMT3 methylates IGF2BP1 at R452, which is critical for IGF2BP1 function in stabilizing the mRNA of HEG1. PRMT3-mediated arginine methylation of IGF2BP1 drives oxaliplatin resistance in hepatocellular carcinoma. |
CRISPR/Cas9 activation library screen, transcriptomic profiling, site-specific mutagenesis at R452, mRNA stability assays, in vitro and in vivo functional validation |
Nature communications |
High |
37024475
|
| 2021 |
FBXO45 E3 ubiquitin ligase promotes IGF2BP1 ubiquitination at Lys190 and Lys450, leading to IGF2BP1 activation and subsequent upregulation of PLK1 expression, driving cell proliferation and liver tumorigenesis. |
Co-immunoprecipitation, ubiquitination assays, site-specific mutagenesis (Lys190/Lys450), IGF2BP1 knockdown rescue experiments, transgenic mouse models |
eLife |
High |
34779401
|
| 2023 |
TRIM29 E3 ubiquitin ligase interacts with IGF2BP1 and induces K48-linked ubiquitination at Lys440 and Lys450, leading to IGF2BP1 protein degradation. IGF2BP1 promotes PD-L1 mRNA stability in a 3'UTR and m6A-dependent manner, and TRIM29-mediated degradation of IGF2BP1 reduces PD-L1 expression to enhance antitumor T-cell immunity. |
Proteomics, co-immunoprecipitation, site-specific ubiquitination assays (K48-linked), mRNA stability assays, in vivo tumor models |
Cancer letters |
Medium |
38029830
|
| 2023 |
USP10 deubiquitinase directly binds, deubiquitinates, and stabilizes IGF2BP1 protein. IGF2BP1 in turn recognizes m6A sites on CPT1A mRNA to enhance its stability, mediating breast cancer metastasis. |
Co-immunoprecipitation, deubiquitination assays, MeRIP-seq, mRNA stability assays, in vitro and in vivo metastasis models |
International journal of biological sciences |
Medium |
36632454
|
| 2021 |
A small molecule inhibitor binds to a hydrophobic surface at the boundary of IGF2BP1 KH3 and KH4 domains and inhibits KRAS RNA binding, reducing KRAS mRNA and protein levels and downstream oncogenic signaling. |
Small molecule screening, direct binding assays to KH3/KH4 domain interface, RNA binding competition assays, wound healing and soft agar growth assays |
RNA biology |
Medium |
34895045
|
| 2014 |
IGF2BP1 drives translation of cIAP1 mRNA in rhabdomyosarcoma cells, protecting them from TNF-α-mediated apoptosis. IGF2BP1 knockdown reduces cIAP1 levels and sensitizes cells to cell death. |
IGF2BP1 knockdown, cIAP1 protein and mRNA quantification, TNF-α-mediated apoptosis assays, in vivo tumor growth experiments with IAP antagonists |
Oncogene |
Medium |
24704827
|
| 2017 |
IGF2BP1 overexpression in human adult erythroblasts causes fetal-like hemoglobin expression by reprogramming at the transcriptional level; mechanistically, IGF2BP1 reduces BCL11A protein expression via posttranscriptional mechanisms (mRNA stability and polysome analysis) to increase fetal hemoglobin. |
Erythroid-specific IGF2BP1 overexpression, hemoglobin quantification by HPLC, mRNA stability and polysome sedimentation assays for BCL11A |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
28652347
|
| 2019 |
IGF2BP1 controls the cargo of melanoma-derived extracellular vesicles (EVs) to promote metastasis. IGF2BP1 knockdown did not alter EV size, number, or protein/RNA concentration, but altered EV mRNA, protein, and miRNA cargo, blocking pre-metastatic niche formation by inhibiting fibronectin deposition and CD45+ cell accumulation in lungs. |
In vivo metastasis models (two models), EV isolation and characterization, RNA-sequencing and proteomics of EVs, IGF2BP1 knockdown/overexpression |
Oncogene |
Medium |
30936459
|
| 2020 |
IGF2BP1 maintains intestinal barrier function by directly binding occludin (Ocln) mRNA and stabilizing it, increasing occludin protein expression. Conditional knockout of IGF2BP1 in intestinal epithelial cells causes impaired tight junction function and colitis; ectopic occludin expression rescues barrier function in IGF2BP1-knockdown cells. |
Conditional knockout mouse (Villin CreERT2:Igf2bp1flox/flox), gut barrier assays, RIP demonstrating direct Ocln mRNA binding, mRNA stability assays, occludin rescue experiments |
The Journal of biological chemistry |
High |
32385106
|
| 2019 |
IGF2BP1 directly binds and stabilizes ETV6/RUNX1 fusion mRNA in t(12;21)-positive acute lymphoblastic leukemia, as shown by RIP enrichment and the reduction of ETV6/RUNX1 mRNA upon IGF2BP1 knockdown. |
RNA immunoprecipitation (RIP), IGF2BP1 knockdown, quantification of ETV6/RUNX1 mRNA in cell lines and primary patient samples |
Blood cells, molecules & diseases |
Medium |
26852652
|
| 2019 |
IGF2BP1 maintains leukemia stem cell properties by stabilizing HOXB4, MYB, and ALDH1A1 mRNAs, as demonstrated by CLIP and PAR-CLIP techniques. Chemical or genetic inhibition of IGF2BP1 decreases tumorigenicity, promotes differentiation, and sensitizes leukemia cells to chemotherapy. |
CLIP, PAR-CLIP, gain- and loss-of-function systems, tumor-initiating potential assays |
Leukemia |
Medium |
31768017
|
| 2020 |
IGF2BP1 promotes SRC kinase activation through a protein-ligand-induced, RNA-independent mechanism, and separately enhances ERK2 expression in an RNA-binding-dependent manner, connecting SRC/MAPK signaling to promote invasive growth in ovarian cancer cells. |
Protein interaction studies, SRC kinase activation assays, RNA-binding-deficient mutants, 3D invasion cultures, intraperitoneal mouse models, SRC/MEK inhibitor rescue experiments |
RNA biology |
Medium |
32876513
|
| 2019 |
IGF2BP1 binds Lnc-THOR RNA; disruption of Lnc-THOR–IGF2BP1 association (by triptonide or Lnc-THOR/IGF2BP1 CRISPR knockout) depletes IGF2BP1 mRNA targets (Myc, IGF2, Gli1) and inhibits NPC cell growth, establishing that Lnc-THOR stabilizes IGF2BP1-dependent target mRNAs. |
Small molecule disruption, CRISPR/Cas9 knockout of Lnc-THOR and IGF2BP1, target mRNA quantification, in vivo xenograft models |
Cancer letters |
Medium |
30503558
|
| 2021 |
mTORC2 phosphorylates IGF2BP1 at Ser181; prevention of this phosphorylation enhances translation and destabilization of c-myc mRNA. Src kinase phosphorylates IGF2BP1 at Tyr396; prevention of Tyr396 phosphorylation causes accumulation of translationally silent IGF2BP1-sequestered mRNA in cytoplasmic granules. |
mTORC2 and Src kinase inhibition, phospho-site mutagenesis (Ser181, Tyr396), reporter assays with CRD sequence, polysome analysis, xenograft models |
Cellular signalling |
Medium |
33388443
|
| 2019 |
IGF2BP1 directly binds MAP1LC3B, ATG3, and ATG5 transcripts (autophagy gene mRNAs), as demonstrated by in silico and biochemical analyses. Intestinal epithelial Imp1 deletion leads to upregulation of Atg5 and increased autophagy flux, and double knockout of Imp1 and Atg7 increases sensitivity to colonic injury, establishing a compensatory relationship between IMP1/IGF2BP1 and autophagy. |
Conditional knockout mice, RNA-IP, in silico binding analysis, DSS colitis models, autophagy flux assays, double-mutant epistasis |
EMBO reports |
Medium |
31061170
|
| 2022 |
IGF2BP1 knockout mice display disorganized neocortical development with loss of cortical marginal cell density and fewer mitotically active cells. In IGF2BP1-null neurons, β-actin mRNA shows increased transcription rates and total protein content but decreased transport and anchoring, demonstrating IGF2BP1 is required for proper β-actin mRNA localization and transport in neurons. |
IGF2BP1 knockout mice, BrdU labeling, endogenously tagged β-actin-MS2 mRNA imaging, mRNA transport and anchoring measurements, transcription rate analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
36067310
|
| 2015 |
Igf2bp1 knockdown in zebrafish reduces retinal ganglion cell (RGC) axonal outgrowth and tectal coverage. RGC-specific expression of a phosphomimetic Igf2bp1 reduces axonal projection density without affecting RGC survival, demonstrating Igf2bp1 is required for axon outgrowth in vivo and that its phosphorylation state modulates this function. |
Morpholino knockdown and phosphomimetic rescue in zebrafish, timelapse imaging of RGC axon outgrowth, photoconvertible fluorescent protein reporter under β-actin 3'UTR |
PloS one |
Medium |
26325373
|
| 2023 |
RPS15 interacts with the KH domain of IGF2BP1, and this complex recognizes and directly binds the 3'UTR of MKK6 and MAPK14 mRNAs in an m6A-dependent manner to promote translation of core p38 MAPK pathway proteins and drive ESCC metastasis. |
CRISPR SAM library screen, Co-IP of RPS15-IGF2BP1, m6A-dependent RIP for MKK6/MAPK14 mRNAs, targeted drug screening, in vitro and in vivo functional assays |
Signal transduction and targeted therapy |
Medium |
37264021
|
| 2019 |
IGF2BP1 promotes LPS-induced NFκB signaling in human macrophages and monocytes. Co-immunoprecipitation showed IGF2BP1 associates with the p65-p52 NFκB complex in nuclei of LPS-treated cells; IGF2BP1 knockdown/knockout inhibits p65-p52 nuclear translocation and NFκB transcriptional activation. |
Co-immunoprecipitation of IGF2BP1 with NFκB p65-p52, nuclear fractionation, shRNA knockdown and CRISPR/Cas9 KO, cytokine ELISA |
Biochemical and biophysical research communications |
Medium |
31000200
|
| 2022 |
MNX1-AS1 lncRNA binds IGF2BP1 and drives its phase separation, which increases IGF2BP1 interaction with the 3'UTR of c-Myc and E2F1 mRNAs to promote their stability, creating a c-Myc/MNX1-AS1/IGF2BP1 positive feedback loop driving cell-cycle progression. |
RNA-protein binding assays, phase separation assays, 3'UTR interaction studies, cell cycle analysis, patient-derived xenograft model |
Cancer research |
Medium |
36214649
|
| 2023 |
MKRN3 interacts with IGF2BP1 (identified by proteomics), and IGF2BP1 in turn interacts with polyadenylate-binding protein family members, positioning IGF2BP1 as a target of MKRN3-mediated regulation of hypothalamic puberty-related gene expression. |
Proteomics interactome analysis, co-immunoprecipitation, Mkrn3 knockout mouse model |
JCI insight |
Low |
37092553
|
| 2023 |
IGF2BP1 directly binds and stabilizes INHBA mRNA; knockdown of IGF2BP1 reduces INHBA expression and attenuates Smad2/3 signaling to suppress ESCC cell invasion and migration. IGF2BP1 also interacts with G3BP1, and G3BP1 knockdown similarly downregulates INHBA-Smad2/3 signaling. |
RIP-seq, mass spectrometry for interacting proteins (identifying G3BP1), gene-specific m6A PCR, RNA stability assays, BTYNB inhibitor treatment |
Experimental hematology & oncology |
Medium |
37644505
|
| 2024 |
ZDHHC1 palmitoylates IGF2BP1 at C337 (S-palmitoylation), which results in downregulated expression of LIPG mRNA via m6A modification, suppressing colorectal cancer cell growth. |
Palmitoylation assays, site-specific mutagenesis (C337), m6A modification analysis, mRNA stability assays, in vitro and in vivo functional studies |
Cancer gene therapy |
Medium |
39069526
|
| 2023 |
IGF2BP1 directly binds and governs expression of SEMA3A and SHMT2 in neuroblastoma cells, modulating their protein levels in small extracellular vesicles (EVs) to regulate pro-metastatic microenvironment formation at potential metastatic organs. |
Unbiased proteomics of EVs, direct binding assays, knockdown/overexpression in immunocompetent mouse NB models, EV isolation and characterization |
Oncogene |
Medium |
36973517
|
| 2017 |
IGF2BP1 is identified as a novel binding partner of p38 MAPK by co-immunoprecipitation followed by mass spectrometry. |
Co-immunoprecipitation, mass spectrometry, in silico domain interaction analysis |
Molecular and cellular biochemistry |
Low |
28497370
|
| 2023 |
IGF2BP1 stabilizes c-MYC mRNA via m6A-dependent binding in gastric cancer cells, promoting aerobic glycolysis and cancer progression. However, a separate study in gastric cancer found IGF2BP1 promotes degradation and reduces translation efficiency of MYC mRNA in an m6A-dependent manner, suggesting a cell-context-dependent switch in IGF2BP1's regulation of MYC. |
RIP, MeRIP, mRNA stability assays, polysome profiling, gain/loss of function in gastric cancer cells |
Experimental cell research / Cancer science |
Low |
35489385 38115228
|
| 2022 |
IGF2BP1 stabilizes EZH2 mRNA in an m6A-dependent manner in neuroendocrine tumor cells, enhancing EZH2 protein levels which then trimethylates H3K27 to silence cell cycle arrest genes and drive proliferation. |
mRNA stability assays, m6A-dependent RIP, IGF2BP1 inhibitor (BTYNB), cell cycle analysis, H3K27me3 ChIP |
Cancers |
Medium |
35565249
|
| 2022 |
Heat treatment promotes IGF2BP1 aggregation specifically in the presence of m6A-modified HPV E7 mRNA, forming heat-induced m6A E7 mRNA-IGF2BP1 granules that are resolved by the ubiquitin-proteasome system, downregulating E7 mRNA and protein. |
Heat treatment assays, m6A mutation experiments, granule imaging, proteasome inhibition assays, in vitro and in vivo HPV carcinogenesis models |
Cell reports |
Medium |
36288717
|
| 2024 |
In zebrafish, Igf2bp1 acts as a reader of METTL16-mediated m6A modifications on mybl2b mRNA (cell-cycle transcription factor); Mettl16 deficiency destabilizes mybl2b mRNA due to lost Igf2bp1 binding, causing G1/S arrest in embryonic hematopoietic stem and progenitor cells. The METTL16-m6A-MYBL2-IGF2BP1 axis is conserved in humans. |
Single-cell RNA-seq cross-species, Mettl16-deficient zebrafish, methyltransferase-dead rescue, m6A-RIP for mybl2b, in vivo HSPC proliferation assays, human cell validation |
The EMBO journal |
High |
38605226
|
| 2023 |
IGF2BP1 synergizes with ETV6-RUNX1 fusion protein in B-ALL by binding and stabilizing the ETV6::RUNX1 fusion transcript, creating a positive feedback loop that constitutively dysregulates TNFα/NFκB and PI3K-Akt oncogenic pathways; co-expression in mouse bone marrow causes pre-leukemic hypercellularity and splenomegaly. |
RIP-seq after IGF2BP1 pulldown, RNA-seq after IGF2BP1 KO, bone marrow transplant mouse model with retroviral co-expression, patient sample validation |
Journal of experimental & clinical cancer research |
High |
37670323
|