HGNC Approved Gene Symbol:E4F1
Cytogenetic location:16p13.3 Genomic coordinates(GRCh38) :16:2,223,591-2,235,742 (from NCBI)
Oncogenic transformation by the adenovirus E1A gene is a consequence of E1A proteins altering the activity or function of cellular transcription factors that are involved in the regulation of cell growth, survival, or differentiation. E4F is one of several cellular transcription factors whose DNA-binding activities are regulated through the action of E1A.Rooney et al. (1998) determined the pattern of tissue expression of the E4F gene in humans and mice.
Using a yeast 2-hybrid system,Fenton et al. (2004) found that RASSF1A (605082) interacted with E4F1, a phosphoprotein involved in cell cycle progression. The 2 proteins formed a complex in vivo in a mouse fibroblast cell line and in a human nonsmall cell lung cancer line. Specific inactivation of RASSF1A by short interfering RNA disrupted the binding of RASSF1A to E4F1 in immunoprecipitation assays. In addition, there was enhanced G1 cell cycle arrest and S-phase inhibition by E4F1 in the presence of RASSF1A.
Chagraoui et al. (2006) found that knockdown of E4f1 levels by RNA interference was sufficient to rescue the clonogenic and repopulating ability of Bmi1 (164831) -/- mouse hematopoietic cells up to 3 months posttransplantation. They concluded that E4F1 is a key modulator of BMI1 activity in primitive hematopoietic cells.
Le Cam et al. (2006) found that human E4F1 functioned as a ubiquitin (191339) E3 ligase for p53 (TP53;191170) both in vitro and in vivo. E4F1-mediated ubiquitylation of p53 occurred at sites distinct from those targeted by MDM2 (164785), competed with PCAF (602303)-induced acetylation of p53, and did not target p53 for proteasomal degradation. E4F1-stimulated p53-ubiquitin conjugates were associated with chromatin, and their stimulation coincided with induction of a p53-dependent transcriptional program specifically involved in cell cycle arrest, but not apoptosis.Le Cam et al. (2006) concluded that E4F1 is a key posttranslational regulator of p53 that plays an important role in the cellular life-or-death decision controlled by p53.
Rooney et al. (1998) determined the chromosomal location of the E4F gene in humans and mice. The mouse chromosomal location of E4f1 was determined by interspecific backcross analysis to be chromosome 17. PCR analysis of DNAs from human/rodent somatic cell hybrids showed 100% concordance for the human gene with chromosome 16. PCR analysis of DNAs from somatic cell hybrids specific for human chromosome 16 and containing defined truncations in the terminal region of 16p localized the E4F gene to a region of approximately 500 kb within 16p13.3.Burn et al. (1996) had likewise mapped a sequence that appeared to be that of E4F to 16p13.3 in exon trapping experiments. A major portion of the gene was located 100 to 200 kb proximal to the start of the polycystic kidney disease gene (601313). By fluorescence in situ hybridization and radiation hybrid mapping,Saccone et al. (1998) assigned the E4F gene to 16p13.3.
Le Cam et al. (2004) generated E4f1 knockout mice. Embryos lacking E4f1 died at the periimplantation stage, and in vitro-cultured mutant blastocysts exhibited defects in mitotic progression, chromosomal missegregation, and increased apoptosis. Consistent with these observations, E4f1 localized to the mitotic spindle during the M phase of early embryos.Le Cam et al. (2004) concluded that E4F1 is crucial during early embryonic cell cycles and functions in mitosis.
Burn, T. C., Connors, T. D., Van Raay, T. J., Dackowski, W. R., Millholland, J. M., Klinger, K. W., Landes, G. M.Generation of a transcriptional map for a 700-kb region surrounding the polycystic kidney disease type 1 (PKD1) and tuberous sclerosis type 1 (TSC2) disease genes on human chromosome 16p13.3. Genome Res. 6: 525-537, 1996. [PubMed:8828041,related citations] [Full Text]
Chagraoui, J., Niessen, S. L., Lessard, J., Girard, S., Coulombe, P., Sauvageau, M., Meloche, S., Sauvageau, G.E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells. Genes Dev. 20: 2110-2120, 2006. [PubMed:16882984,images,related citations] [Full Text]
Fenton, S. L., Dallol, A., Agathanggelou, A., Hesson, L., Ahmed-Choudhury, J., Baksh, S., Sardet, C., Dammann, R., Minna, J. D., Downward, J., Maher, E. R., Latif, F.Identification of the E1A-regulated transcription factor p120(E4F) as an interacting partner of the RASSF1A candidate tumor suppressor gene. Cancer Res. 64: 102-107, 2004. [PubMed:14729613,related citations] [Full Text]
Le Cam, L., Lacroix, M., Ciemerych, M. A., Sardet, C., Sicinski, P.The E4F protein is required for mitotic progression during embryonic cell cycles. Molec. Cell. Biol. 24: 6467-6475, 2004. [PubMed:15226446,images,related citations] [Full Text]
Le Cam, L., Linares, L. K., Paul, C., Julien, E., Lacroix, M., Hatchi, E., Triboulet, R., Bossis, G., Shmueli, A., Rodriguez, M. S., Coux, O., Sardet, C.E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation. Cell 127: 775-788, 2006. [PubMed:17110336,related citations] [Full Text]
Rooney, R. J., Daniels, R. R., Jenkins, N. A., Gilbert, D. J., Rothammer, K., Morris, S. W., Higgs, D. R., Copeland, N. G.Chromosomal location and tissue expression of the gene encoding the adenovirus E1A-regulated transcription factor E4F in humans and mice. Mammalian Genome 9: 320-323, 1998. [PubMed:9530632,related citations] [Full Text]
Saccone, S., Sandy, P., Meroni, G., Gostissa, M., Della Valle, G., Del Sal, G.Assignment of the E1A-regulated transcription factor E4F gene (E4F1) to human chromosome band 16p13.3 by in situ hybridization and somatic cell hybrids. Cytogenet. Cell Genet. 82: 99-100, 1998. [PubMed:9763670,related citations] [Full Text]
Alternative titles; symbols
HGNC Approved Gene Symbol: E4F1
Cytogenetic location: 16p13.3 Genomic coordinates(GRCh38) : 16:2,223,591-2,235,742(from NCBI)
Oncogenic transformation by the adenovirus E1A gene is a consequence of E1A proteins altering the activity or function of cellular transcription factors that are involved in the regulation of cell growth, survival, or differentiation. E4F is one of several cellular transcription factors whose DNA-binding activities are regulated through the action of E1A. Rooney et al. (1998) determined the pattern of tissue expression of the E4F gene in humans and mice.
Using a yeast 2-hybrid system, Fenton et al. (2004) found that RASSF1A (605082) interacted with E4F1, a phosphoprotein involved in cell cycle progression. The 2 proteins formed a complex in vivo in a mouse fibroblast cell line and in a human nonsmall cell lung cancer line. Specific inactivation of RASSF1A by short interfering RNA disrupted the binding of RASSF1A to E4F1 in immunoprecipitation assays. In addition, there was enhanced G1 cell cycle arrest and S-phase inhibition by E4F1 in the presence of RASSF1A.
Chagraoui et al. (2006) found that knockdown of E4f1 levels by RNA interference was sufficient to rescue the clonogenic and repopulating ability of Bmi1 (164831) -/- mouse hematopoietic cells up to 3 months posttransplantation. They concluded that E4F1 is a key modulator of BMI1 activity in primitive hematopoietic cells.
Le Cam et al. (2006) found that human E4F1 functioned as a ubiquitin (191339) E3 ligase for p53 (TP53; 191170) both in vitro and in vivo. E4F1-mediated ubiquitylation of p53 occurred at sites distinct from those targeted by MDM2 (164785), competed with PCAF (602303)-induced acetylation of p53, and did not target p53 for proteasomal degradation. E4F1-stimulated p53-ubiquitin conjugates were associated with chromatin, and their stimulation coincided with induction of a p53-dependent transcriptional program specifically involved in cell cycle arrest, but not apoptosis. Le Cam et al. (2006) concluded that E4F1 is a key posttranslational regulator of p53 that plays an important role in the cellular life-or-death decision controlled by p53.
Rooney et al. (1998) determined the chromosomal location of the E4F gene in humans and mice. The mouse chromosomal location of E4f1 was determined by interspecific backcross analysis to be chromosome 17. PCR analysis of DNAs from human/rodent somatic cell hybrids showed 100% concordance for the human gene with chromosome 16. PCR analysis of DNAs from somatic cell hybrids specific for human chromosome 16 and containing defined truncations in the terminal region of 16p localized the E4F gene to a region of approximately 500 kb within 16p13.3. Burn et al. (1996) had likewise mapped a sequence that appeared to be that of E4F to 16p13.3 in exon trapping experiments. A major portion of the gene was located 100 to 200 kb proximal to the start of the polycystic kidney disease gene (601313). By fluorescence in situ hybridization and radiation hybrid mapping, Saccone et al. (1998) assigned the E4F gene to 16p13.3.
Le Cam et al. (2004) generated E4f1 knockout mice. Embryos lacking E4f1 died at the periimplantation stage, and in vitro-cultured mutant blastocysts exhibited defects in mitotic progression, chromosomal missegregation, and increased apoptosis. Consistent with these observations, E4f1 localized to the mitotic spindle during the M phase of early embryos. Le Cam et al. (2004) concluded that E4F1 is crucial during early embryonic cell cycles and functions in mitosis.
Burn, T. C., Connors, T. D., Van Raay, T. J., Dackowski, W. R., Millholland, J. M., Klinger, K. W., Landes, G. M.Generation of a transcriptional map for a 700-kb region surrounding the polycystic kidney disease type 1 (PKD1) and tuberous sclerosis type 1 (TSC2) disease genes on human chromosome 16p13.3. Genome Res. 6: 525-537, 1996. [PubMed: 8828041] [Full Text: https://doi.org/10.1101/gr.6.6.525]
Chagraoui, J., Niessen, S. L., Lessard, J., Girard, S., Coulombe, P., Sauvageau, M., Meloche, S., Sauvageau, G.E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells. Genes Dev. 20: 2110-2120, 2006. [PubMed: 16882984] [Full Text: https://doi.org/10.1101/gad.1453406]
Fenton, S. L., Dallol, A., Agathanggelou, A., Hesson, L., Ahmed-Choudhury, J., Baksh, S., Sardet, C., Dammann, R., Minna, J. D., Downward, J., Maher, E. R., Latif, F.Identification of the E1A-regulated transcription factor p120(E4F) as an interacting partner of the RASSF1A candidate tumor suppressor gene. Cancer Res. 64: 102-107, 2004. [PubMed: 14729613] [Full Text: https://doi.org/10.1158/0008-5472.can-03-2622]
Le Cam, L., Lacroix, M., Ciemerych, M. A., Sardet, C., Sicinski, P.The E4F protein is required for mitotic progression during embryonic cell cycles. Molec. Cell. Biol. 24: 6467-6475, 2004. [PubMed: 15226446] [Full Text: https://doi.org/10.1128/MCB.24.14.6467-6475.2004]
Le Cam, L., Linares, L. K., Paul, C., Julien, E., Lacroix, M., Hatchi, E., Triboulet, R., Bossis, G., Shmueli, A., Rodriguez, M. S., Coux, O., Sardet, C.E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation. Cell 127: 775-788, 2006. [PubMed: 17110336] [Full Text: https://doi.org/10.1016/j.cell.2006.09.031]
Rooney, R. J., Daniels, R. R., Jenkins, N. A., Gilbert, D. J., Rothammer, K., Morris, S. W., Higgs, D. R., Copeland, N. G.Chromosomal location and tissue expression of the gene encoding the adenovirus E1A-regulated transcription factor E4F in humans and mice. Mammalian Genome 9: 320-323, 1998. [PubMed: 9530632] [Full Text: https://doi.org/10.1007/s003359900758]
Saccone, S., Sandy, P., Meroni, G., Gostissa, M., Della Valle, G., Del Sal, G.Assignment of the E1A-regulated transcription factor E4F gene (E4F1) to human chromosome band 16p13.3 by in situ hybridization and somatic cell hybrids. Cytogenet. Cell Genet. 82: 99-100, 1998. [PubMed: 9763670] [Full Text: https://doi.org/10.1159/000015075]
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