| 1993 |
E2F2 (E2F-2) was cloned and found to share 46% amino acid identity with E2F1. The DNA binding domain and retinoblastoma (Rb) protein binding domain functions are conserved. E2F2 DNA binding activity is dramatically enhanced by complementation with HeLa cell E2F components, consistent with E2F binding DNA as a heterodimer, and anti-E2F-2 antibodies cross-react with purified HeLa cell E2F. |
cDNA cloning, DNA binding assays, antibody cross-reactivity, complementation assays with SDS-PAGE-purified HeLa cell E2F components |
Molecular and cellular biology |
High |
8246995
|
| 1997 |
The E2F2 promoter contains E-box elements that function as Myc-responsive activation sites and E2F binding sites that mediate negative (repressive) regulation in quiescent cells. Both elements contribute to the cell-growth-dependent control of E2F2 expression, similar to regulation of the E2F1 gene promoter. |
Promoter reporter assays, deletion/mutation analysis, growth stimulation experiments |
Molecular and cellular biology |
Medium |
9271400
|
| 2001 |
E2F2 is required for immunologic self-tolerance. E2F2-deficient T lymphocytes exhibit enhanced TCR-stimulated proliferation and a lower activation threshold. Rather than functioning as a transcriptional activator, E2F2 appears to function as a transcriptional repressor of genes required for S phase entry, particularly E2F1. |
E2f2 knockout mice, T cell proliferation assays, TCR stimulation, immunophenotyping |
Immunity |
High |
11754817
|
| 2001 |
Combined loss of E2F1 and E2F2 results in profound effects on hematopoietic cell proliferation, B-cell differentiation, and T-cell tolerance/proliferation thresholds. E2F1/E2F2 double-knockout T cells exhibit more rapid entry into S phase and extensive proliferation in response to subthreshold antigenic stimulation, and double-knockout mice are highly predisposed to tumor development. |
E2f1/E2f2 double-knockout mice, cell cycle analysis, antigenic stimulation, tumor monitoring |
Molecular and cellular biology |
High |
11713289
|
| 2001 |
Drosophila E2f2 loss is viable but causes female sterility associated with failure to confine DNA synthesis to gene amplification sites in follicle cells. E2f2 mutant follicle cells inappropriately initiate genomic DNA replication instead of restricting synthesis to chorion gene amplification loci. Replication proteins ORC2, CDC45L, and ORC5 redistribute throughout the nucleus in E2f2 mutants. RT-PCR showed increased Orc5 mRNA in E2f2 mutants, indicating E2f2 represses pre-RC gene expression. |
Drosophila E2f2 mutant genetics, BrdU incorporation, immunofluorescence localization of ORC2/CDC45L/ORC5, RT-PCR |
Development (Cambridge, England) |
High |
11748144
|
| 2001 |
Forced expression of E2F2 in PC12 cells (neuronal differentiation model) inhibited dedifferentiation and cell cycle re-entry upon NGF removal, and induced apoptosis instead. E2F2 converted reversibly differentiated neurons to a terminally differentiated, NGF-dependent state. Endogenous E2F2 levels increase in PC12 cells in response to NGF. |
Gain-of-function E2F2 overexpression in PC12 cells, NGF removal assay, cell cycle re-entry assays, apoptosis assays |
Oncogene |
Medium |
11526501
|
| 2002 |
E2F1, E2F2, and E2F3 each contribute individually to Rb-deficiency-induced unscheduled proliferation in vivo. In the developing lens and retina of Rb-/- embryos, loss of E2F2 reduces ectopic DNA replication. E2F2 loss partially reduces unscheduled DNA replication in the CNS but has no effect on apoptosis in Rb-null embryos, demonstrating functional specificity among E2Fs. |
Compound Rb/E2f knockout mice, BrdU incorporation (ectopic proliferation), TUNEL (apoptosis), tissue-specific analysis |
Cell growth & differentiation |
High |
12065245
|
| 2002 |
E2F2 and E2F3 can transcriptionally activate the p14(ARF) promoter, even in the absence of consensus E2F binding sites. Deletion and site-directed mutagenesis indicate E2F can regulate ARF both by direct DNA binding and indirectly, possibly via tethering by Sp1-like factors. |
Transient transfection reporter assays, promoter deletion and site-directed mutagenesis |
Biochemical and biophysical research communications |
Medium |
11883935
|
| 2002 |
ARF induction in response to oncogenic Ras and viral E1A oncoprotein is not significantly affected in E2F1-/-, E2F2-/-, or E2F1/2 double-knockout MEFs. ARF is upregulated normally in all cases, indicating ARF activation by oncogenic stress can occur by E2F1- and E2F2-independent mechanisms. |
Primary E2f1/E2f2 knockout MEFs, oncogenic Ras/E1A overexpression, ARF western blot and transcription assays |
Oncogene |
Medium |
12082524
|
| 2003 |
E2F-2 binds to the ECE-1b promoter specifically, as demonstrated by EMSA. The -338A allele of the ECE-1b promoter shows increased affinity for E2F-2 compared to the -338C allele, and is associated with increased promoter activity in reporter assays. |
EMSA (electrophoretic mobility shift assay), transient transfection reporter assay |
Human molecular genetics |
Medium |
12566389
|
| 2003 |
Drosophila RBF1 forms complexes with both E2F1/DP and E2F2/DP that cooperate to repress pre-replication complex (pre-RC) gene expression in follicle cells, thereby confining DNA synthesis to gene amplification sites. Reducing Orc2, Orc5, or Mcm2 gene dose by half suppresses the ectopic genomic replication phenotype of E2f2 mutants (genetic epistasis). E2F1 and E2F2 repressors function redundantly for some genes in the embryo but have context-dependent relative contributions. |
Drosophila genetics (epistasis by dosage reduction), RT-PCR, DNA microarray analysis of pre-RC gene transcripts |
Molecular and cellular biology |
High |
12612083
|
| 2003 |
E2F2 transgenic mice (driven by Emu/pim1 promoter targeting thymic epithelial cells) develop cortical thymomas from 20 weeks, demonstrating that E2F2 deregulation promotes cell division and oncogenic transformation of thymic epithelial cells. In contrast, E2F1 transgenic mice do not develop cortical thymomas under the same promoter, indicating functional specificity. |
Transgenic mouse generation, tumor monitoring, immunohistochemistry (cytokeratin, ER-TR4), thymocyte subset analysis |
The Journal of biological chemistry |
Medium |
14684733
|
| 2003 |
Loss of both E2F1 and E2F2 in pancreatic cells leads to increased rates of DNA replication, apoptosis, and severe pancreatic atrophy. DNA replication and cell cycle control genes are upregulated in E2F1/E2F2 compound-mutant pancreas, indicating these genes are normally repressed by E2F1/E2F2 activity. E2F1/E2F2 activity is also required for maintenance of differentiated pancreatic phenotypes, as ductal and adipocyte marker genes were upregulated while pancreatic cell markers were downregulated. |
E2f1/E2f2 compound-mutant mice, gene expression profiling, histology, cell cycle analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
14566047 15146237
|
| 2004 |
The Drosophila Myb-MuvB complex contains E2F2, DP, RBF1, RBF2, LIN-52, L(3)MBT, and Rpd3 (HDAC), identified by affinity chromatography fractionation of embryo extracts. Members of this complex localize to promoters and co-repress transcription of developmentally regulated genes. |
Affinity chromatography of Drosophila embryo extracts, co-purification, chromatin immunoprecipitation, transcriptional repression assays |
Genes & development |
High |
15545624
|
| 2005 |
HPV31 E7 activates E2F2 transcription specifically in differentiating (suprabasal) keratinocytes by inhibiting HDAC binding to the E2F2 promoter, as demonstrated by chromatin immunoprecipitation. siRNA knockdown of E2F2 confirmed that E2F2 expression is required for HPV replication but not for cell proliferation in this context. |
Chromatin immunoprecipitation (ChIP), siRNA knockdown, HPV replication assays, differentiated keratinocyte model |
The EMBO journal |
High |
15861133
|
| 2005 |
Directed expression of E2F2 (but not E2F1, E2F3, or E2F5) in neonatal cardiomyocytes induces mitotic cell division without triggering apoptosis, while E2F1 and E2F3 induce both S-phase entry and apoptosis. E2F2 and E2F4 both induce S-phase entry, but only E2F2 results in actual mitotic division. E2F2/E2F4 expression down-regulate pro-apoptotic genes that are activated by E2F1/E2F3. |
Adenovirus-mediated gene transfer, BrdU incorporation, TUNEL apoptosis assay, quantitative RT-PCR of cell cycle and apoptotic genes |
Circulation research |
High |
15718499
|
| 2005 |
Overexpression of E2F2 in nonproliferating human corneal endothelial cells (ex vivo adenoviral delivery) induces G1-to-S phase progression and increased cell density without significant apoptosis, as shown by BrdU incorporation and specular microscopy. |
Adenoviral E2F2 overexpression in ex vivo human corneas, BrdU incorporation, specular microscopy, TUNEL assay |
Investigative ophthalmology & visual science |
Medium |
16186339
|
| 2006 |
E2f1, E2f2, and E2f3 are required for oncogene-mediated transformation. Their combined inactivation elevates p21(CIP1) protein levels and causes cell cycle arrest at G1/S and G2/M. Loss of p21(CIP1) (but not p53) restores G1/S entry in triple-knockout cells. Loss of p53 (but not p21) allows cells to progress through both G1/S and mitosis and renders cells sensitive to transformation, indicating the critical function of E2F1-3 is in negative regulation of the p53-p21(CIP1) axis. |
Compound E2f conditional knockout MEFs, cell synchronization, p21/p53 inactivation by genetic crossing or dominant-negative, oncogene transformation assays |
The Journal of biological chemistry |
High |
17008321
|
| 2007 |
E2F2 functions as a transcriptional repressor of cell cycle genes to establish G0 quiescence. Loss of E2F2 causes T cells and MEFs to enter S phase early and undergo accelerated cell division. A large set of E2F target genes (Mcm's, cyclins, Cdc2a) that are normally silent in G0 are actively expressed in quiescent E2F2-knockout cells. ChIP analysis shows E2F2 occupies promoters of these genes in G0, confirming direct repressive role. Classic E2F activators E2F1 and E2F3 are largely dispensable for this quiescence maintenance. |
E2f2 knockout mice, S phase entry assays (BrdU), ChIP, shRNA knockdown of E2F3, compound E2F1/E2F2 double-knockout |
Cell cycle (Georgetown, Tex.) |
High |
19066456
|
| 2007 |
Combined inactivation of E2f1, E2f2, and E2f3 in MEFs activates p53 and induces p21(CIP1), leading to inhibition of CDK activity and Rb phosphorylation, Rb/E2F-mediated target gene repression, and severe proliferative block. Inactivation of p53 in E2f1/2/3-deficient cells prevents p21 induction, restores CDK activity and Rb phosphorylation, and allows near-normal E2F target gene expression and response to growth signals. |
Conditional triple knockout MEFs, p53 conditional knockout, immunoblot for CDK activity and Rb phosphorylation, RT-PCR of E2F targets |
Molecular and cellular biology |
High |
17167174
|
| 2007 |
Loss of E2f2 accelerates Myc-driven T cell lymphomagenesis in a bitransgenic mouse model, while loss of E2f1 or E2f3 has no significant effect. Loss of a single copy of E2f2 also accelerates tumorigenesis (haploinsufficiency). Myc-overexpressing T cells are more resistant to apoptosis in the absence of E2f2, and reintroduction of E2F2 into tumor cells increases apoptosis and inhibits tumorigenesis, identifying E2f2 as a tumor suppressor that modulates apoptosis. |
Bitransgenic mouse model (MMTV-Myc × E2f KO), tumor progression monitoring, apoptosis assays, E2F2 reintroduction into tumor cells |
Proceedings of the National Academy of Sciences of the United States of America |
High |
17881568
|
| 2007 |
p53 and Rb (via E2Fs) repress survivin transcription in normal human melanocytes through direct promoter binding. E2F2 specifically binds a novel E2F site in the survivin promoter and negatively regulates survivin expression. Mutation of either the p53 or E2F binding sites is sufficient to increase survivin promoter activity. |
ChIP assay, promoter-reporter assays with site-directed mutation, siRNA knockdown of E2F2 |
Carcinogenesis |
Medium |
17916908
|
| 2007 |
E2f-2 is the major pRb-associated E2F in end-stage red cells (erythroblasts) and the predominant E2F detected at key target gene promoters during terminal erythroid differentiation. E2f-2 loss restores terminal erythroid maturation (including enucleation) to Rb-null red cells. Deletion of E2f-2 also extends the lifespan of Rb-null mice. Aberrant S-phase entry of Rb-null erythroblasts is inhibited by E2f-2 deletion. |
Compound Rb/E2f-2 knockout mice, ChIP at target gene promoters, cell cycle analysis, enucleation assays, survival analysis |
Molecular and cellular biology |
High |
17923680
|
| 2008 |
EKLF/KLF1 directly occupies the proximal E2f2 promoter in erythroid progenitor cells in vivo. Loss of EKLF reduces E2f2 mRNA and protein levels in early erythroid progenitors, leading to a delay in G1-to-S phase transition. EKLF binding sites in the E2f2 promoter lie in a region of EKLF-dependent DNase I sensitivity. |
Eklf-knockout mice, ChIP (EKLF occupancy at E2f2 promoter), DNase I hypersensitivity, RT-PCR, western blot, cell cycle analysis |
Molecular and cellular biology |
High |
18852285
|
| 2008 |
Directed expression of E2F2 in adult mouse hearts (via adenoviral vector) induces proliferation of cardiomyocytes in vivo, without increasing apoptosis. E2F2 in vivo causes strong induction of cyclin A and cyclin E while not affecting CDK inhibitor p21. E2F2 also down-regulates pro-apoptotic genes caspase-6 and apaf-1. |
Adenoviral E2F2 delivery in mice, histological section analysis, quantitative RT-PCR, western blot of cell cycle regulatory proteins |
Cardiovascular research |
Medium |
18628254
|
| 2009 |
GATA-1 forms a tricomplex with pRb and E2F-2 during terminal erythroid differentiation. This interaction requires a LXCXE motif conserved in GATA-1 orthologs (absent from other GATA family members). The GATA-1/pRb/E2F-2 complex stalls cell proliferation and steers erythroid precursors toward terminal differentiation. FOG-1 can disrupt this complex by displacing pRb/E2F-2 from GATA-1. A GATA-1 mutant unable to bind pRb fails to inhibit proliferation and causes embryonic lethality by anemia. |
Co-immunoprecipitation, domain mapping (LXCXE motif), GATA-1 mutant mouse models, in vitro disruption assay with FOG-1, cell proliferation assays |
PLoS biology |
High |
19513100
|
| 2009 |
EKLF/KLF1 directly activates E2f2 through a novel intronic enhancer containing conserved CACC, GATA, and E-BOX elements. EKLF occupies this E2f2 enhancer in vivo (ChIP). Loss of EKLF causes aberrant S-phase entry, and additional genetic depletion of Rb (epistasis) partially restores normal cell cycle dynamics, establishing a causal link between reduced E2f2 and the EKLF cell cycle defect. |
ChIP (EKLF occupancy at E2f2 intronic enhancer), Rb/EKLF double-knockout epistasis, cell cycle analysis |
The Journal of biological chemistry |
High |
19457859
|
| 2009 |
E2F2 directly binds the ECE-1b promoter in endothelial cells (confirmed by ChIP) and activates ECE-1b transcription (confirmed by promoter-reporter assay). Loss of E2F2 leads to decreased ECE-1b mRNA, elevated membranous ECE-1 isoforms (ECE-1a, -1c, -1d), deregulated ECE-1 activity, increased vascular contractility, and higher blood pressure in E2F2-null mice. Sam68 co-immunoprecipitates with E2F2, occupies the ECE-1b promoter (ChIP), and represses E2F2-mediated ECE-1b transcription. |
ChIP (E2F2 and Sam68 at ECE-1b promoter), promoter-reporter assays, co-immunoprecipitation (Sam68-E2F2), tail-cuff blood pressure measurement in E2F2-null mice, ex vivo aortic ring contractility |
Circulation |
High |
19752322
|
| 2009 |
miR-24 directly regulates E2F2 expression by binding seedless but highly complementary sequences in the E2F2 3'UTR. Enhanced proliferation from antagonizing miR-24 is abrogated by knocking down E2F2, and miR-24-insensitive E2F2 rescues miR-24-mediated inhibition of proliferation, demonstrating that E2F2 is a critical functional target of miR-24. |
miRNA overexpression/antagonism, E2F2 knockdown rescue experiment, miR-24-resistant E2F2 rescue, microarray-based target identification |
Molecular cell |
High |
19748357
|
| 2010 |
E2F1/E2F2 deficiency in differentiating bone marrow-derived macrophages results in accelerated DNA replication and cellular division, accompanied by early expression of DNA replication and cell cycle regulators. Rapid proliferation is followed by induction of a DNA damage response and p21(CIP1)-dependent senescence. Senescence is not triggered in the absence of DNA replication, establishing a causal link between E2F1/E2F2 loss, DNA hyper-replication, and senescence. |
Compound E2f1/E2f2 knockout bone marrow differentiation, BrdU incorporation, gene expression profiling, aphidicolin (replication inhibitor) experiment, p21 pathway analysis |
Oncogene |
High |
20676136
|
| 2010 |
Drosophila dE2F2 (E2F2), together with net E2F activity (assessed by dDp mutation), inhibits p53-independent IR-induced apoptosis in larval imaginal discs. dE2F1 promotes IR-induced p53-independent apoptosis and is required for transcriptional induction of the pro-apoptotic gene hid after irradiation when p53 is mutated. These two E2F homologs have opposing effects on p53-independent apoptosis. |
Drosophila genetics (E2f2 and Dp mutants), transcriptional reporters (hid), irradiation, p53 mutation background |
Developmental biology |
Medium |
20659447
|
| 2011 |
E2F2 is required for adult hepatocyte proliferation and timely liver regeneration after partial hepatectomy. E2F2-knockout hepatocytes exhibit a reduced rate of S-phase entry and delayed liver regeneration. Transcriptome analysis shows that genes for cell cycle, apoptosis, and wound-healing response are absent in posthepatectomized E2F2-/- mice. |
E2f2-knockout mice, partial hepatectomy model, BrdU incorporation, transcriptome analysis |
American journal of physiology. Gastrointestinal and liver physiology |
Medium |
21527726
|
| 2013 |
E2F2 occupies promoters of a large number of cell cycle and DNA metabolism genes during T cell quiescence (ChIP-chip genome-wide analysis). E2F2 and CREB cooperate in transcriptional repression of a subset of target genes (Mcm5, Chk1). CREB knockdown (siRNA), dominant-negative KCREB expression, or mutation of the CRE motif in the Mcm5 promoter relieves E2F2-mediated repression. This repression is retinoblastoma-independent. |
ChIP-chip (genome-wide), expression profiling, luciferase reporter assays, siRNA knockdown (CREB), dominant-negative CREB, CRE site mutation |
Nucleic acids research |
High |
24038359
|
| 2013 |
Drosophila Myb-null cytokinesis failure (binucleate cells) is suppressed by loss of E2F2 or Mip130 (dREAM complex subunits), indicating that transcriptional repression by the dREAM complex requires E2F2 for its full activity. The Myb-null phenotype is sensitive to dosage of E2F2, Mip120, Caf1, and Lin-52. Reduction of histone variant H2Av/H2A.z also suppresses the Myb-null phenotype, implicating H2A.z in dREAM-mediated transcriptional repression. |
Drosophila genetics (Myb-null with E2F2/dREAM subunit mutations), quantitative phenotypic readout (binucleate cell frequency), H2Av dosage reduction |
Molecular and cellular biology |
Medium |
23438598
|
| 2013 |
E2f2 (but not E2f1 or E2f3) is required and sufficient for cone photoreceptor apoptosis in Rb/p107 double-null retinas, demonstrating a direct, E2f1-independent apoptotic function. E2f2-induced cone death is p53-dependent (in contrast to E2f1-dependent apoptosis in other neurons which is p53-independent). E2f2 deletion rescues cone survival in Rb/p107-null retinas. |
Compound Rb/p107/E2f knockout mice, TUNEL apoptosis assay, genetic rescue experiments |
Cell death and differentiation |
High |
23558950
|
| 2013 |
ALY (THO complex 4) associates with DNA-bound E2F2 and represses its transcriptional activity. ALY influences the expression of over 400 genes, including 98 genes with consensus E2F motifs, as determined by expression microarrays in ALY-overexpressing or ALY-silenced HEK293T cells expressing E2F2. |
Co-immunoprecipitation (ALY-E2F2 interaction), expression microarrays (ALY overexpression and siRNA silencing in E2F2-expressing cells) |
Molecular & cellular proteomics : MCP |
Medium |
23297349
|
| 2015 |
Loss of E2F1 and E2F2 together (but not individually) prevents replicative stress in the pancreas. Combined inactivation leads to unscheduled DNA replication, DNA damage response activation, and p53-mediated mitochondrial apoptosis causing pancreatic atrophy and diabetes. Suppression of DNA replication in vivo with aphidicolin significantly inhibits the p53 pathway in double-knockout pancreas. Targeted p53 inactivation abrogates cellular apoptosis and prevents organ involution, establishing a causal E2F-p53 regulatory axis. |
E2f1/E2f2 double-knockout mice, aphidicolin treatment (in vivo replication suppression), p53 triple-knockout mice, DNA damage marker analysis, apoptosis assays |
Cell death and differentiation |
High |
25656653
|
| 2015 |
E2F1 and E2F2 are transcriptionally induced in neuronal cells after DNA damage (genotoxic treatment), leading to increased protein levels via de novo synthesis. E2F1/E2F2 accumulate at sites of oxidative and UV-induced DNA damage and interact with γH2AX. E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase, and induces histone acetylation following genotoxic insult. Ablation of E2F1 and E2F2 leads to DNA lesion accumulation, increased apoptosis, and reduced DNA repair capacity. |
Genotoxic treatment, de novo protein synthesis assays, co-immunoprecipitation (E2F2-γH2AX and E2F2-GCN5), immunofluorescence (E2F2 accumulation at damage sites, Rad51 foci), siRNA knockdown, cell viability assays |
Cell cycle (Georgetown, Tex.) |
High |
25892555
|
| 2016 |
E2F-2 is required for efficient erythroblast enucleation and nuclear condensation during terminal erythroid differentiation. Citron Rho-interacting kinase (CRIK) is induced in erythroblasts in an E2F-2-dependent manner, and CRIK activity promotes efficient erythroblast enucleation and nuclear condensation. E2F-2 deletion impairs nuclear condensation in mature erythroblasts. |
E2f-2 knockout mice, enucleation assays, transcriptome profiling of E2F-2-null erythroblasts, functional inhibition/activation of CRIK |
Molecular and cellular biology |
Medium |
27795297
|
| 2016 |
BRD4 inhibition (by JQ1) identifies E2F2 as a direct downstream target of BRD4 in liver cancer cells, confirmed by ChIP assay. Loss-of-function of E2F2 in liver cancer cells recapitulates BRD4 inhibition effects on cell cycle arrest. |
ChIP assay (BRD4 at E2F2 promoter), siRNA knockdown of E2F2, JQ1 treatment with gene expression analysis |
Oncotarget |
Medium |
27081696
|
| 2018 |
E2F2 directly binds the promoters of STAT1 and MyD88 (confirmed by ChIP and luciferase assays) and upregulates their expression, facilitating formation of STAT1/MyD88 complexes and AKT activation. This E2F2-STAT1/MyD88-AKT axis drives inflammatory cytokine (IL-1α, IL-1β, TNF-α) production in rheumatoid arthritis synovial fibroblasts. Silencing STAT1/MyD88 or inactivating AKT attenuates cytokine induction by E2F2. |
ChIP-PCR, luciferase reporter assay, co-immunoprecipitation (STAT1-MyD88 complex), western blot, E2f2-knockout mouse collagen arthritis model, siRNA knockdown |
Arthritis research & therapy |
High |
30286793
|
| 2021 |
E2F2 directly binds the CPT2 promoter (confirmed by ChIP) and represses its transcription, inhibiting fatty acid oxidation. E2f2-knockout mice show enhanced fatty acid oxidation and increased CPT2 expression. E2f2 knockdown in liver recapitulates this, while E2f2 overexpression has opposing effects. This E2F2-CPT2 axis creates a lipid-rich environment promoting hepatocarcinogenesis. |
ChIP (E2F2 at CPT2 promoter), E2f2-knockout mice, shRNA knockdown in liver, E2f2 overexpression, fatty acid oxidation assays, DEN/HFD hepatocarcinogenesis model |
Cancer research |
High |
33771899
|
| 2021 |
E2F2 transcriptionally activates PFKFB4 by directly binding its promoter (confirmed by ChIP and luciferase assay), activating the PI3K/AKT signaling pathway to promote glioma cell glycolysis and malignant progression. PFKFB4 knockdown mitigates E2F2-driven glioma metastasis and glycolysis. |
ChIP, luciferase assay, PFKFB4 knockdown, E2F2 overexpression/knockdown, glycolysis assays, in vivo tumor growth/metastasis models |
Life sciences |
Medium |
33774025
|
| 2021 |
B-Myb directly transactivates E2F2, and E2F2 in turn directly transactivates B-Myb, forming a reciprocal feed-forward transcriptional loop in colorectal cancer. B-Myb and E2F2 physically interact and co-occupy each other's promoters. Both B-Myb and E2F2 are required for ERK and AKT signaling pathway activation in colorectal cancer cells. |
Co-immunoprecipitation (B-Myb/E2F2 interaction), ChIP (B-Myb and E2F2 at each other's promoters), luciferase reporter assay, siRNA knockdown, in vivo orthotopic tumor model |
Oncogene |
High |
34316028
|
| 2022 |
E2F2 undergoes ubiquitination and proteasomal degradation via the atypical E3 ligase ZFP91. The natural product bufalin promotes E2F2-ZFP91 complex formation (identified by human proteome microarray and Co-IP/SILAC quantitative proteomics), leading to E2F2 polyubiquitination via K48-linked ubiquitin chains and degradation. E2F2 degradation causes transcriptional suppression of oncogenes including c-Myc, CCNE1, CCNE2, MCM5 and CDK1. |
Human proteome microarray, Co-IP with SILAC-based quantitative proteomics, ubiquitination assay (K48-linkage), proteasome inhibitor experiments, gene expression analysis |
EBioMedicine |
High |
36375317
|
| 2010 |
Loss of E2F2 in E2F2-deficient T lymphocytes leads to deregulated Aryl-hydrocarbon-receptor (Ahr) pathway. Proliferating E2F2-/- T cells express significantly higher levels of Aip, Ahr, and Arnt. E2F2 directly regulates the Aip gene promoter (binding confirmed), and E2F2-/- T cells show increased sensitivity to TCDD-triggered apoptosis. ChIP showed E2F2 binding to Ahr and Arnt promoters as well. |
Differential proteomics (E2F2-/- vs WT T cells), ChIP (E2F2 at Aip/Ahr/Arnt promoters), TCDD treatment apoptosis assay |
Molecular & cellular proteomics : MCP |
Medium |
20573986
|
| 2022 |
E2F2 forms part of a core transcription regulatory circuitry with B-Myb and FOXM1 in lung adenocarcinoma; these three factors positively correlate in expression, physically associate, mutually transactivate each other, and regulate similar downstream gene cascades. E2F2 promotes LUAD growth in orthotopic mouse models. |
Co-immunoprecipitation (E2F2/B-Myb/FOXM1 interaction), ChIP, luciferase reporter assay, siRNA knockdown, orthotopic mouse tumor model |
International journal of biological sciences |
Medium |
35844795
|