ArticleJournal of virology1997
Human adenovirus early region 4 open reading frame 1 genes encode growth-transforming proteins that may be distantly related to dUTP pyrophosphatase enzymes.
Article in Journal of virology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 74 citations in OpenAlex.
- The adenovirus E4orf1 protein initiates a feedback loop involving insulin and growth factor receptors, AKT, and NF-κB, leading to abnormal DNA content in infected cells.PLoS pathogens · 2025Article
- In Silico Intensive Analysis for the E4 Gene Evolution of Human Adenovirus Species D.Journal of microbiology (Seoul, Korea) · 2024Article
- The human adenovirus PI3K-Akt activator E4orf1 is targeted by the tumor suppressor p53.Journal of virology · 2024Article
- Viral dUTPases: Modulators of Innate Immunity.Biomolecules · 2022Review
- Characterization of the First Genome of Porcine mastadenovirus B (HNU1 Strain) and Implications on Its Lymphoid and Special Origin.Virologica Sinica · 2020Article
- Characterization of the adipogenic protein E4orf1 from adenovirus 36 through an in silico approach.Journal of molecular modeling · 2020Article
- Genomic and phylogenetic analysis of two guinea pig adenovirus strains recovered from archival lung tissue.Virus research · 2020Article
- Hepatic Expression of Adenovirus 36 E4ORF1 Improves Glycemic Control and Promotes Glucose Metabolism Through AKT Activation.Diabetes · 2017Article
- Targeting Nucleotide Biosynthesis: A Strategy for Improving the Oncolytic Potential of DNA Viruses.Frontiers in oncology · 2017Review
- Herpesviruses dUTPases: A New Family of Pathogen-Associated Molecular Pattern (PAMP) Proteins with Implications for Human Disease.Pathogens (Basel, Switzerland) · 2016Review
- Adenovirus E4-ORF1 Dysregulates Epidermal Growth Factor and Insulin/Insulin-Like Growth Factor Receptors To Mediate Constitutive Myc Expression.Journal of virology · 2015Article
- Hijacking Dlg1 for oncogenic phosphatidylinositol 3-kinase activation in human epithelial cells is a conserved mechanism of human adenovirus E4-ORF1 proteins.Journal of virology · 2014Article
- The human adenovirus E4-ORF1 protein subverts discs large 1 to mediate membrane recruitment and dysregulation of phosphatidylinositol 3-kinase.PLoS pathogens · 2014Article
- Human herpesviruses-encoded dUTPases: a family of proteins that modulate dendritic cell function and innate immunity.Frontiers in microbiology · 2014Article
- Article
- Review
- Genomic and bioinformatics analysis of human adenovirus type 37: new insights into corneal tropism.BMC genomics · 2008Article
- Article
- A new crucial protein interaction element that targets the adenovirus E4-ORF1 oncoprotein to membrane vesicles.Journal of virology · 2007Article
- New genes from old: redeployment of dUTPase by herpesviruses.Journal of virology · 2005Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
An essential oncogenic determinant of subgroup D human adenovirus type 9 (Ad9), which uniquely elicits estrogen-dependent mammary tumors in rats, is encoded by early region 4 open reading frame 1 (E4 ORF1). Whereas Ad9 E4 ORF1 efficiently induces transformed foci on the established rat embryo fibroblast cell line CREF, the related subgroup A Ad12 and subgroup C Ad5 E4 ORF1s do not (R. T. Javier, J. Virol. 68:3917-3924, 1994). In this study, we found that the lack of transforming activity associated with non-subgroup D adenovirus E4 ORF1s in CREF cells correlated with significantly reduced protein levels compared to Ad9 E4 ORF1 in these cells. In the human cell line TE85, however, the non-subgroup D adenovirus E4 ORF1s produced protein levels higher than those seen in CREF cells as well as transforming activities similar to that of Ad9 E4 ORF1, suggesting that all adenovirus E4 ORF1 polypeptides possess comparable cellular growth-transforming activities. In addition, searches for known proteins related to these novel viral transforming proteins revealed that the E4 ORF1 proteins had weak sequence similarity, over the entire length of the E4 ORF1 polypeptides, with a variety of organismal and viral dUTP pyrophosphatase (dUTPase) enzymes. Even though adenovirus E4 ORF1 proteins lacked conserved protein motifs of dUTPase enzymes or detectable enzymatic activity, E4 ORF1 and dUTPase proteins were predicted to possess strikingly similar secondary structure arrangements. It was also established that an avian adenovirus protein, encoded within a genomic location analogous to that of the human adenovirus E4 ORF1s, was a genuine dUTPase enzyme. Although no functional similarity was found for the E4 ORF1 and dUTPase proteins, we propose that human adenovirus E4 ORF1 genes have evolved from an ancestral adenovirus dUTPase and, from this structural framework, developed novel transforming properties.
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