ArticleOncogene2004
Nuclear localization of the adenovirus E4orf4 protein is mediated through an arginine-rich motif and correlates with cell death.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Identification of the Potential Role of the E4orf4 Protein in Adenovirus A, B, C, and D Groups in Cancer Therapy: Computational Approaches.Molecular biotechnology · 2025Article
- Cancer Treatment Goes Viral: Using Viral Proteins to Induce Tumour-Specific Cell Death.Cancers · 2019Review
- Antitumor and antibacterial properties of virally encoded cationic sequences.Biologics : targets & therapy · 2019Article
- The AMPK agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), but not metformin, prevents inflammation-associated cachectic muscle wasting.EMBO molecular medicine · 2018Article
- The Human Adenovirus Type 5 E4orf4 Protein Targets Two Phosphatase Regulators of the Hippo Signaling Pathway.Journal of virology · 2015Article
- Interregional Coevolution Analysis Revealing Functional and Structural Interrelatedness between Different Genomic Regions in Human Mastadenovirus D.Journal of virology · 2015Article
- Review
- Viral genes as oncolytic agents for cancer therapy.Cellular and molecular life sciences : CMLS · 2015Review
- Interaction of adenovirus type 5 E4orf4 with the nuclear pore subunit Nup205 is required for proper viral gene expression.Journal of virology · 2014Article
- Adenovirus E4orf4 protein-induced death of p53-/- H1299 human cancer cells follows a G1 arrest of both tetraploid and diploid cells due to a failure to initiate DNA synthesis.Journal of virology · 2013Article
- Identification of the adenovirus E4orf4 protein binding site on the B55α and Cdc55 regulatory subunits of PP2A: Implications for PP2A function, tumor cell killing and viral replication.PLoS pathogens · 2013Article
- NoD: a Nucleolar localization sequence detector for eukaryotic and viral proteins.BMC bioinformatics · 2011Article
- Genetic analysis of B55alpha/Cdc55 protein phosphatase 2A subunits: association with the adenovirus E4orf4 protein.Journal of virology · 2011Article
- The cytosolic tail of the Golgi apyrase Ynd1 mediates E4orf4-induced toxicity in Saccharomyces cerevisiae.PloS one · 2010Article
- Nucleolar proteomics and viral infection.Proteomics · 2010Review
- Adenovirus protein E4orf4 induces premature APCCdc20 activation in Saccharomyces cerevisiae by a protein phosphatase 2A-dependent mechanism.Journal of virology · 2010Article
- Proteomics analysis of the nucleolus in adenovirus-infected cells.Molecular & cellular proteomics : MCP · 2010Article
- Localization and importance of the adenovirus E4orf4 protein during lytic infection.Journal of virology · 2009Article
- Identification of a new human adenovirus protein encoded by a novel late l-strand transcription unit.Journal of virology · 2007Article
- Adenovirus E4orf4 hijacks rho GTPase-dependent actin dynamics to kill cells: a role for endosome-associated actin assembly.Molecular biology of the cell · 2006Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adenovirus E4orf4 protein induces p53-independent death of human cancer cells by a mechanism requiring interactions with the Balpha subunit of protein phosphatase 2A. When expressed alone E4orf4 localizes predominantly in the nucleus, although significant levels are also present in the cytoplasm. While tyrosine phosphorylation of E4orf4 and recruitment of Src have been linked with E4orf4 cytoplasmic cell death functions, little is known about the functions of E4orf4 in the nucleus. In this study, we identified an arginine-rich motif (E4ARM; residues 66-75) that is necessary and sufficient for nuclear and nucleolar localization. This motif, which is highly homologous to the arginine-rich nuclear and nucleolar localization motif of some lentiviral proteins, was shown to target heterologous proteins to the nucleus and to nucleoli, functions found to be dependent on the overall charge of the motif rather than on specific residues. Furthermore, mutation of arginine residues to alanines but not to lysines in E4ARM was shown to block such targeting activity and, when introduced into full-length E4orf4, to decrease induction of cell death. Finally, coexpression of the ARM motifs of E4orf4, HIV-1 Tat or Rev along with full-length E4orf4 was seen to decrease E4orf4-dependent cell killing. Thus it appears that targeting of E4orf4 to the nucleus and cell nucleoli by E4ARM is an important component of E4orf4-induced cell death.
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