Disease relevance of E4F1

• In addition to the E4 promoter, E4F1 interacts with other adenovirus early promoters and thus may be involved in the co-ordinate expression of E1a-inducible early viral genes [1].

High impact information on E4F1

• E4F1 and PCAF mediate mutually exclusive posttranslational modifications of p53 [2].
• Here, we identify the p53-associated factor E4F1, a ubiquitously expressed zinc-finger protein first identified as a cellular target of the viral oncoprotein E1A, as an atypical ubiquitin E3 ligase for p53 that modulates its effector functions without promoting proteolysis [2].
• Together, these findings identify E4F1 as a key modulator of BMI1 activity in primitive hematopoietic cells [3].
• Here we report the identification of E4F1, an inhibitor of cellular proliferation, as a novel BMI1-interacting partner in hematopoietic cells [3].
• Previous experiments have identified E4F, an inducible cellular factor that binds to sequences in the adenovirus E4 promoter that are critical for E1A-dependent transcriptional activation [4].

Biological context of E4F1

• E4F1, a possible inducer of cell growth arrest, was markedly increased only in ER alpha-positive VSMCs by estrogens in both microarray and RT-PCR analyses [5].
• Collectively, our data reveal that E4F1 is a key posttranslational regulator of p53, which modulates its effector functions involved in alternative cell fates: growth arrest or apoptosis [2].
• These and other results suggest that the E4 promoter may be comprised solely of multiple E4F1 binding sites and a TATA box [1].
• A cellular transcription factor E4F1 interacts with an E1a-inducible enhancer and mediates constitutive enhancer function in vitro [1].
• Mouse embryos lacking E4F die at an early developmental stage, whereas enforced expression of E4F1 in various cell lines inhibits cell cycle progression [6].

Anatomical context of E4F1

• Assignment of the E1A-regulated transcription factor E4F gene (E4F1) to human chromosome band 16p13.3 by in situ hybridization and somatic cell hybrids [7].
• This result suggests that E1A induction of the E4 promoter in HeLa cells is primarily mediated by E4F [8].
• Embryos lacking E4F die at the peri-implantation stage, while in vitro-cultured E4F(-/-) blastocysts exhibit defects in mitotic progression, chromosomal missegregation, and increased apoptosis [9].

Associations of E4F1 with chemical compounds

• E4F1, a novel estrogen-responsive gene in possible atheroprotection, revealed by microarray analysis [5].
• Here we demonstrate that p120(E4F) interacts with HDAC1 in vivo and in vitro, and that E4F-mediated transcriptional repression is alleviated by the HDAC inhibitor trichostatin A or by overexpressing Gam1 [10].

Regulatory relationships of E4F1

• Blocking of E4F1 using siRNA suppressed estrogenic inhibition of ER alpha-positive VSMC proliferation [5].
• This E4F1-FHL2 association occurs in the nuclear compartment and inhibits the capacity of E4F1 to block cell proliferation [6].

Other interactions of E4F1

• E4F1 is therefore considered one of the estrogen-responsive genes involving ER alpha-mediated inhibition of VSMC proliferation and may play an important role in estrogen-related atheroprotection of human aorta [5].

Analytical, diagnostic and therapeutic context of E4F1

• To address this issue, we generated E4F knockout mice by gene targeting [9].

References