E2F3 (E2F transcription factor 3)

2005-07-01   Roderick AF MacLeod  , Stefan Nagel  

DSMZ-Deutsche Sammlung von, Mikroorganismen und Zellkulturen, Inhoffenstr. 7B, D-38124 Braunschweig, Germany

Identity

HGNC
LOCATION
6p22.3
LOCUSID
ALIAS
E2F-3
FUSION GENES

DNA/RNA

Atlas Image
Schematic diagram of the E2F3 gene comprising 7 exons (in blue). Exons 1a or 1b are used alternatively to produce variants E2F3A or E2F3B, respectively. The sizes in base pairs (bp) of exons (above) and introns (below) are shown.

Description

The gene has 7 exons (two alternative exons 1) and 6 introns comprising 91545 bp.

Transcription

Transcription takes place in a centromeric -> telomeric orientation. The length of the processed mRNA is about 4744 bp. EMBL lists two alternativly spliced forms other than those concerning exons 1a/b.

Pseudogene

2q33-q35, 17q11-q12

Proteins

Atlas Image
Schematic diagram of E2F3 protein structure. E2F3A is shown in the upper part, E2F3B below. The proteins differ in their N-terminal regions comprising 132 and 6 amino acid residues, respectively. N: nuclear localization sequence, LZ: leucine zipper (blue), RBD: pRB binding domain (light blue). DNA binding domain (yellow), dimerization domain (red), transactivation domain (green). The positions of amino acid residues are indicated.

Description

E2F3A comprises 465 amino acid residues (49 kDa), E2F3B comprises 334 amino acid residues.

Expression

ubiquitous

Localisation

nuclear

Function

E2F3 is a sequence-specific transcription factor implicated in cell cycle regulation (S-phase). It is a transcriptional activator for E2F-responsive genes. E2F proteins heterodimerize with DP proteins and are subject to inhibition by binding to the pocket domain of retinoblastoma protein (pRB). Phosphorylation of pRB sets E2F proteins free to regulate their target genes.

Homology

E2F transcription factor family consists of E2F-proteins (E2F1-6) and DP-proteins (DP1, DP2).

Mutations

Note

Gene mutations have not been described hitherto.

Germinal

Not known

Somatic

Not known

Implicated in

Entity name
amp(6)(p22)
Note
Medium-to-high-level genomic amplification sometimes resulting in HSR formation and believed to target E2F3 which lies within the common amplified region (see image below). Genomic amplification may not be required for over-expression.
Disease
Notably, bladder and prostate cancers.
Prognosis
Associated with invasiveness in bladder cancer, and with poor survival in prostate cancer. Circa 33% of primary transitional cell carcinomas of the bladder overexpress nuclear E2F3 protein.
Cytogenetics
Presumptive target of genomic amplification at 6p22 in bladder cancer where it effects E2F3 overexpression (as exemplified by the bladder cancer cell lines 5637 and HT-1367). However, E2F3 may not be the only target gene inside the common amplified region.
Hybrid gene
Not yet reported
Atlas Image
Genomic amplification of E2F3: FISH image shows HT-1376 bladder cancer cell line (DSMZ acc 397) hybridized with a BAC clone (RPMI-99F1) covering the E2F3 locus at 6p22.3. (See breakpoint diagram below for map.) Note high level genomic amplification comprising multiple tandemly repeated copies of E2F3 via formation of an homogeneously staining region (HSR) in a marker chromosome - a hallmark of oncogene activity. Similar findings have been reported in both primary bladder and prostate cancers. Analysis of E2F3 protein has confirmed overexpression in cell lines evidencing genomic amplification, including HT-1376 as well as 5637 (DSMZ acc 35) and TCC-SUP (DSMZ acc 377).
Entity name
t(6;9)(p22;p13)
Note
Observed in a DLBCL cell line: yet to be described clinically.
Prognosis
Unknown
Cytogenetics
Breakpoint lies upstream of E2F3 and juxtaposes upstream (regulatory) region of PAX5.
Hybrid gene
Not yet reported
See below
Oncogenesis
E2F3 behaves like a classical oncogene and is subject to upregulation via genomic amplification in bladder and prostate cancers. Upregulated E2F3 stimulates cycle progression and proliferation. E2F3 transcription is induced by MYC and these together conspire to promote G1/S-phase transition. This activity is negatively regulated by binding of the E2F transactivation domain to RB1 or p107. In prostate cancer, oncogenesis directed by E2F3 may be mediated by the polycomb group protein Enhancer of Zeste Homolog gene 2 (EZH2). E2F3 may also activate survivin transcription.
In Hodgkin lymphoma which, though lacking recurrent chromosomal rearrangements at 6p22, shows a pattern of gene dysregulation reminiscent of prostate cancer, E2F3 regulates HLXB9 expression which in turn drives IL-6 expression thought to play a central role in this enigmatic tumor.
E2F3 may also act as a tumor suppressor though the supporting evidence is tentative. Thus, while E2F3 loss results in centrosome defects associated with aneuploidy and promotes metastasis of medullary thyroid carcinoma, E2F3 -/- mice show no excess tumor incidence. Furthermore, loss of E2F3 has been associated with suppression of pituitary tumors.

Breakpoints

Atlas Image
Figure depicts location of sole E2F3 breakpoint described hitherto, lying approximately 50-150 Kbp upstream of the transcription unit as detected in a complex t(6;9)(p22;p13) in a DLBCL cell line. The upstream region of E2F3 is thus juxtaposed with the upstream regulatory region of PAX5. Figure shows genes flanking E2F3 together with RPCI-11 library clones.

Article Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 1871
MIM: 600427
HGNC: 3115
Ensembl: ENSG00000112242

Variants:

dbSNP: 1871
ClinVar: 1871
TCGA: ENSG00000112242
COSMIC: E2F3

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000112242ENST00000346618O00716
ENSG00000112242ENST00000535432O00716
ENSG00000112242ENST00000613242A0A087X0B6

Expression (GTEx)

0
5
10
15
20

Pathways

PathwaySourceExternal ID
Cell cycleKEGGko04110
Pancreatic cancerKEGGko05212
GliomaKEGGko05214
Prostate cancerKEGGko05215
MelanomaKEGGko05218
Bladder cancerKEGGko05219
Chronic myeloid leukemiaKEGGko05220
Small cell lung cancerKEGGko05222
Non-small cell lung cancerKEGGko05223
Cell cycleKEGGhsa04110
Pathways in cancerKEGGhsa05200
Pancreatic cancerKEGGhsa05212
GliomaKEGGhsa05214
Prostate cancerKEGGhsa05215
MelanomaKEGGhsa05218
Bladder cancerKEGGhsa05219
Chronic myeloid leukemiaKEGGhsa05220
Small cell lung cancerKEGGhsa05222
Non-small cell lung cancerKEGGhsa05223
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Hepatitis BKEGGhsa05161
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
Cell cycle - G1/S transitionKEGGhsa_M00692
Cell cycle - G1/S transitionKEGGM00692
Signal TransductionREACTOMER-HSA-162582
Signaling by NOTCHREACTOMER-HSA-157118
Pre-NOTCH Expression and ProcessingREACTOMER-HSA-1912422
Pre-NOTCH Transcription and TranslationREACTOMER-HSA-1912408
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic G1-G1/S phasesREACTOMER-HSA-453279
G1 PhaseREACTOMER-HSA-69236
Cyclin D associated events in G1REACTOMER-HSA-69231
Regulation of DNA replicationREACTOMER-HSA-69304
Association of licensing factors with the pre-replicative complexREACTOMER-HSA-69298
Mitotic G2-G2/M phasesREACTOMER-HSA-453274
G2 PhaseREACTOMER-HSA-68911
M/G1 TransitionREACTOMER-HSA-68874
DNA Replication Pre-InitiationREACTOMER-HSA-69002
Assembly of the pre-replicative complexREACTOMER-HSA-68867
CDC6 association with the ORC:origin complexREACTOMER-HSA-68689
DNA ReplicationREACTOMER-HSA-69306
Cellular responses to stressREACTOMER-HSA-2262752
Cellular SenescenceREACTOMER-HSA-2559583
Oncogene Induced SenescenceREACTOMER-HSA-2559585
Oxidative Stress Induced SenescenceREACTOMER-HSA-2559580
Endocrine resistanceKEGGko01522
Endocrine resistanceKEGGhsa01522
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224

References

Pubmed IDYearTitleCitations
377756192024MiR-210-3p enhances intermittent hypoxia-induced tumor progression via inhibition of E2F3.2
381941582024Transcription factor E2F3 activates CDC25B to regulate DNA damage and promote mitoxantrone resistance in stomach adenocarcinoma.0
383809572024FTO promotes the progression of retinoblastoma through YTHDF2-dependent N6-methyladenosine modification in E2F3.0
377756192024MiR-210-3p enhances intermittent hypoxia-induced tumor progression via inhibition of E2F3.2
381941582024Transcription factor E2F3 activates CDC25B to regulate DNA damage and promote mitoxantrone resistance in stomach adenocarcinoma.0
383809572024FTO promotes the progression of retinoblastoma through YTHDF2-dependent N6-methyladenosine modification in E2F3.0
361620092023Interaction of E2F3a and CASP8AP2 Regulates Histone Expression and Chemosensitivity of Leukemic Cells.0
367382822023CircKRT14 upregulates E2F3 by interacting with miR-1256 to act as an oncogenic factor in esophageal cancer.0
372873692023Circ_001422 aggravates osteosarcoma progression through targeting miR-497-5p/E2F3 axis.0
374999292023E2F3 induces DNA damage repair, stem-like properties and therapy resistance in breast cancer.0
361620092023Interaction of E2F3a and CASP8AP2 Regulates Histone Expression and Chemosensitivity of Leukemic Cells.0
367382822023CircKRT14 upregulates E2F3 by interacting with miR-1256 to act as an oncogenic factor in esophageal cancer.0
372873692023Circ_001422 aggravates osteosarcoma progression through targeting miR-497-5p/E2F3 axis.0
374999292023E2F3 induces DNA damage repair, stem-like properties and therapy resistance in breast cancer.0
344182322022Long noncoding RNA plasmacytoma variant translocation 1 promotes progression of colorectal cancer by sponging microRNA-152-3p and regulating E2F3/MAPK8 signaling.13

Citation

Roderick AF MacLeod ; Stefan Nagel

E2F3 (E2F transcription factor 3)

Atlas Genet Cytogenet Oncol Haematol. 2005-07-01

Online version: http://atlasgeneticsoncology.org/gene/40384/js/lib/gene-fusions-explorer/case-report-explorer/