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FLASH GENE
Symbol E2F1 contributors: mct/shn - updated : 26-07-2017
HGNC name E2F transcription factor 1
HGNC id 3113
Location 20q11.22      Physical location : 32.263.292 - 32.274.210
Synonym name
  • retinoblastoma-associated protein 1
  • PRB-binding protein E2F-1
  • retinoblastoma-binding protein 3
  • Synonym symbol(s) RBAP1, RBBP3, E2F-1, PBR3
    DNA
    TYPE functioning gene
    STRUCTURE 10.92 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure for TERT promoter
    MAPPING cloned Y linked N status confirmed
    Map cen - D20S195 - D20S890 - E2F1 - D20S878 - D20S601 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 2722 - 437 - 2009 19763085
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumearinnercochlea highly
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systemuteruscervix highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal DNA binding domain
  • putative leucine zippers
  • a carboxyterminal domain of interaction with pRB
  • cyclin binding domain
  • a HCFC1-binding site
  • HOMOLOGY
    interspecies ortholog to E2f1, Rattus norvegicus
    ortholog to E2f1, Mus musculus
    ortholog to E2F1, Pan troglodytes
    Homologene
    FAMILY
  • E2F/DP family of transcription factor
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • controlling genes regulating S phase entry and DNA synthesis
  • involved in apoptosis (signal for apoptosis)
  • may be having the potential to repress transcription of numerous genes
  • can directly bind to and activate the promoter of DIABLO, a mitochondrial proapoptotic gene, through the E2F1-binding sites BS2 and BS3 and so promoting p53-independent apoptosis
  • modulate the expression of MAP3K5 and some of the cellular functions of MAP3K5 may be under the control of E2F transcription factors
  • contributes to the transcriptional activation of the KIR3DL1 gene
  • plays an important role in regulating TNFSF11 transcription through binding to the E2F consensus binding site
  • acting as a critical transcription factor that regulates TNFSF11 gene transcription
  • could exert a strong influence over the susceptibility to oncogenic transformation
  • controls multiple cellular activities through transcriptional regulation of its target genes
  • mediator of cell death, can eliminate latent neoplastic cells through apoptosis
  • plays an important role in modulating neuronal death in response to excitotoxicity and cerebral ischemia
  • first transcription factor regulating FOXO expression, providing a link between E2F and FOXO proteins in the control of cell fate
  • activates BNIP3 and the intrinsic death pathway in ventricular myocytes)
  • E2F1 and KLF6 show cooperation in activating the DAPK2 promoter
  • requires SFRS2 to switch the alternative splicing profile of various apoptotic genes such as CFLAR, CASP8 and 9 and BCL2L1, towards the expression of pro-apoptotic splice variants
  • having an important role for transcriptional activation of FGFR1 promoter
  • role of E2F1-CCNE1-CCNE2 circuit in coronary smooth muscle cell proliferation
  • key positive regulator of cell proliferation and its activity is altered in essentially all cancers
  • essential transcription factor for tapasin (TAPBP)
  • involved in cell cycle regulation through their cyclin-dependent interactions with pocket proteins, including the tumor suppressor RB
  • important role for E2F1 in the transcriptional regulation of tapasin in untransformed and HER-2/neu-transformed fibroblasts
  • plays a crucial role in transcriptional control of the HELLS gene and the decrease of HELLS expression in senescent cells is related to the repression of E2F1
  • participates in TP53-mediated DNA damage response and might have a checkpoint function to limit overactive TP53
  • in contrast to E2F1 and E2F3, which sensitize to death, E2F4 plays a crucial protective role in neuronal death evoked by DNA damage, hypoxia, and global ischemic insult
  • E2F1 contributes to mammalian glucose homeostasis by directly controlling hepatic gluconeogenesis
  • CELLULAR PROCESS cell cycle
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • Rb-E2F1 apoptotic pathway responds to mitochondrial stress induced by hypermethylation of 12S rRNA in mitochondrial ribosomes
  • a component
  • MCPH1–E2F1 complex might be important in the maintenance of genomic integrity and correct response to DNA damage
  • RB1/RBBP8/CTBP1/E2F1 complex plays a critical role in ZNF350 transcriptional repression, and loss of this repression may contribute to cellular sensitivity of DNA damage, ultimately leading to carcinogenesis
  • BRCA1/E2F1/RBBP8 binding to ATM promoter activates ATM transcription
  • INTERACTION
    DNA binding to E2F1-binding sites BS2 and BS3
    RNA
    small molecule
    protein
  • Cyclin A/CDK2 (
  • Rb and adenovirus E4 proteins (
  • DP1 (
  • CBP (
  • BRCA1 (
  • NF-kappaB (
  • DDB (
  • Necdin, NDN (
  • transformation/transcription domain-associated protein, TRRAP (
  • E2FBP1 (
  • Sp1 (
  • ubiquitin-protein ligase SCFSKP2 (
  • DNA (cytosine-5-)-methyltransferase 1, DNMT1 (
  • neural proliferation, differentiation and control 1, NPDC1 (
  • p553 (
  • CHK2 checkpoint homolog (S. pombe), CHEK2 (
  • p107 (RBL1, p130 (RBL2) binding
  • inducing TP73 and indirectly TP53
  • TRAF2 (downregulation of TRAF2)inducing apoptosis
  • inducing SIVA
  • PHB
  • RB1 and CEBP1 important in C/EBPepsilon-induced terminal granulocytic differentiation
  • RHOBTB2 (novel direct target of E2F1 with roles in cell cycle and apoptosis)
  • positive transcriptional regulator for CTNND1
  • poly (ADP-ribose) polymerase 1, PARP1 (
  • Activating signal cointegrator-2A, SC-2 (
  • HAT Tip60 (
  • ACTR (
  • PURA (
  • E2F-associated phosphoprotein, EAPP (
  • ASPP1 and ASPP2 (
  • p21 (
  • MDM2 (
  • NRP1 (positively regulates NRP1 during cerebral ischemia)
  • DUSP2, binds to its consensus sequence in the promoter and transactivates the DUSP2 promoter
  • host cell factor 1, HCF1(
  • lymphoid enhancer-binding factor 1, LEF1 (
  • COPS2 (acts as a corepressor for E2F1 and is involved in cell cycle regulation)
  • with E2F1 contribute to ATM-dependent phosphorylation of p53 and apoptosis in cells expressing E1A
  • GSK3 beta (
  • microcephalin 1, MCPH1 (
  • CUX1 and E2F1 regulate coordinated expression of the mitotic complex genes ECT2, RACGAP1, and KIF23 in S phase
  • HCFC1 (E2F1 HCFC1-binding site can modulate both up and down the ability of E2F1 to induce apoptosis indicating that HCFC1 association with E2F1 is a regulator of E2F1-induced apoptosis) (
  • RRP1B, is an E2F1-specific transcriptional target (RRP1B is required for the expression of certain E2F1 proapoptotic target genes and the induction of apoptosis by DNA-damaging agents)
  • is necessary, but not sufficient, to activate PCYT1A expression when this factor is over-expressed
  • E2F1-CDKN1C interaction mediated by two E2F domains (a central E2F1 domain interacts directly with CDKN1C, whereas a C-terminal E2F1 domain interacts with CDKN1C via interaction with Rb)
  • DP-4 (
  • negatively regulates IRF3 transcription through binding to the E2F consensus binding site)
  • physically interacts with the HELLS promoter by binding to each of the two putative binding sites and transactivates the HELLS promoter
  • negatively regulate Wnt/CTNNB activity in colorectal cancers
  • activation of CTNNBIP1 by E2F1 is required for E2F1 to inhibit CTNNB activity
  • BIRC2 dramatically increases the transcriptional activity of E2F1 on synthetic and CCNE promoters
  • CDKN2A is a modulator of transcription and apoptosis through controlling the expression of two major transcription regulators, HNRNPD and E2F1
  • has an inhibitory role in TP53-mediated apoptosis
  • KLF15 inhibits mesangial cell proliferation, possibly by regulating the expression of cell cycle regulation proteins through E2F1
  • E2F1 is a substrate for NEDD8 post-translational modification (NEDDylation results in decreased E2F1 stability, lower transcriptional activity and slower cell growth)
  • RB1 protein selectively represses specific E2F1 target genes via a TAAC element in senescent cells
  • RSLID1 is a direct target of E2F1
  • SENP8 promoted the interaction between E2F1 and its cofactor MCPH1, which is required for TP73 induction
  • DOK1 is regulated mainly by the transcription factor E2F1
  • binds to the BCL2L11 promoter at multiple sites
  • SRSF2 is a new transcriptional target of E2F1 and both proteins cooperate to induce apoptosis in non-small cell lung carcinoma
  • NELL2 is a novel target gene of E2F1, which is a key regulator of cell proliferation
  • UHRF2 directly interacts with E2F1, and is required for E2F1 induction of apoptosis and transcription of a number of important apoptotic regulators)
  • E2F1/FOXO1/FOXO3 cooperation is a regulatory mechanism that places E2F1 apoptotic activity under the control of survival signaling
  • direct downstream target gene of ELL (ELL enhanced E2F1 deacetylation via recruitment of HDAC1
  • TFDP3 is likely involved in prostate cancer cell survival by suppressing apoptosis induced by E2F1
  • RORA bound to the heptad repeat and marked box region of E2F1 and suppressed E2F1-regulated transcription in epithelial cells
  • likely a regulatory role for KDM2A in breast cancer cell invasion and migration, through the regulation of E2F1 function
  • role of E2F1 in the regulation of RRM2B expression in DNA damage response (DDR)
  • E2F1 can promote colorectal cancer proliferation, migration, invasion and metastasis by regulating RRM2 transactivation
  • UCHL5 expression is induced by E2F1, and its level rises in G1/S transition and S phase, suggesting a positive feedback loop between UCHL5 and E2F1
  • deubiquitylase PSMD14 stabilizes E2F1 protein through binding to and deubiquitylating E2F1, and hyperactivated PSMD14-E2F1 regulation may contribute to the development of liver cancer 6)
  • STAU2 is likely an anti-apoptotic protein that could be involved in DNA replication and/or maintenance of genome integrity and its expression is regulated by E2F1 via the ATR signaling pathway
  • NOVA2 integrated splicing decisions in order to regulate PPPARG and E2F1 activities
  • mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity
  • cell & other
    REGULATION
    induced by E2F1 (direct target of E2F1)
    inhibited by downregulated in post-mitotic neurons by interaction with NDN and proteolysis through the ubiquitin-proteasome pathway
    ARF (
    repressed by a putative coiled-coil domain of prohibitin
    CDK8
    ZNF346 (represses E2F1 transcriptional activity in association with repression of cyclin A expression and inhibition of G1/S transition)
    Other regulated by the prohibitin (in response to specific signaling cascade)
    transcriptional repressor of TERT
    regulated by p14(ARF) (
    regulated DP-4 during the DNA damage response (
    regulated by DNA topoisomerase IIbeta binding protein 1, TopBP1 in response to DNA damage (
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in metastatic tissues from hormone-resistant prostate cancer patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    E2F1-DUSP2 cascade in cancer cell killing may provide a molecular basis for cancer therapeutic intervention
    diabetetype 2 
    specifically targeting E2F1 in the liver could be an interesting strategy for therapies against type 2 diabetes
    ANIMAL & CELL MODELS
    E2f1-deficient mice exhibit defects in apoptosis and are rather prone to tumorigenesis