ArticleThe Journal of cell biology2000
Adenovirus E4 open reading frame 4-induced apoptosis involves dysregulation of Src family kinases.
Article in The Journal of cell biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 77 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
- The adenoviral E4orf3/4 is a regulatory polypeptide with cell transforming properties in vitro.Tumour virus research · 2023Article
- Article
- Manipulation of Focal Adhesion Signaling by Pathogenic Microbes.International journal of molecular sciences · 2021Review
- The adenoviral protein E4orf4: a probing tool to decipher mechanical stress-induced nuclear envelope remodeling in tumor cells.Cell cycle (Georgetown, Tex.) · 2020Article
- Adenoviral protein E4orf4 interacts with the polarity protein Par3 to induce nuclear rupture and tumor cell death.The Journal of cell biology · 2020Article
- Selective elimination of cancer cells by the adenovirus E4orf4 protein in a Drosophila cancer model: a new paradigm for cancer therapy.Cell death & disease · 2019Article
- Fine-tuning of actin dynamics by the HSPB8-BAG3 chaperone complex facilitates cytokinesis and contributes to its impact on cell division.Cell stress & chaperones · 2017Article
- A Role for the Chaperone Complex BAG3-HSPB8 in Actin Dynamics, Spindle Orientation and Proper Chromosome Segregation during Mitosis.PLoS genetics · 2015Article
- The Human Adenovirus Type 5 E4orf4 Protein Targets Two Phosphatase Regulators of the Hippo Signaling Pathway.Journal of virology · 2015Article
- Review
- Viral genes as oncolytic agents for cancer therapy.Cellular and molecular life sciences : CMLS · 2015Review
- NTPDASE4 gene products cooperate with the adenovirus E4orf4 protein through PP2A-dependent and -independent mechanisms and contribute to induction of cell death.Journal of virology · 2014Article
- A functional interplay between the small GTPase Rab11a and mitochondria-shaping proteins regulates mitochondrial positioning and polarization of the actin cytoskeleton downstream of Src family kinases.The Journal of biological chemistry · 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
- The adenovirus E4orf4 protein induces a unique mode of cell death while inhibiting classical apoptosis.Cell cycle (Georgetown, Tex.) · 2013Article
- Structure- and modeling-based identification of the adenovirus E4orf4 binding site in the protein phosphatase 2A B55α subunit.The Journal of biological chemistry · 2013Article
- E4orf4 induces PP2A- and Src-dependent cell death in Drosophila melanogaster and at the same time inhibits classic apoptosis pathways.Proceedings of the National Academy of Sciences of the United States of America · 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
- Preparation of cell-lines for conditional knockdown of gene expression and measurement of the knockdown effects on E4orf4-induced cell death.Journal of visualized experiments : JoVE · 2012Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adenoviral early region 4 open reading frame 4 (E4orf4) death factor induces p53-independent apoptosis in many cell types and appears to kill selectively transformed cells. Here we show that expression of E4orf4 in transformed epithelial cells results in early caspase-independent membrane blebbing, associated with changes in the organization of focal adhesions and actin cytoskeleton. Evidence that E4orf4 can associate with and modulate Src family kinase activity, inhibiting Src-dependent phosphorylation of focal adhesion kinase (FAK) and paxillin while increasing phosphorylation of cortactin and some other cellular proteins, is presented. Furthermore, E4orf4 dramatically inhibited the ability of FAK and c-src to cooperate in induction of tyrosine phosphorylation of cellular substrates, suggesting that E4orf4 can interfere with the formation of a signaling complex at focal adhesion sites. Consistent with a functional role for E4orf4-Src interaction, overexpression of activated c-src dramatically potentiated E4orf4-induced membrane blebbing and apoptosis, whereas kinase dead c-src constructs inhibited E4orf4 effects on cell morphology and death. Moreover treatment of E4orf4-expressing cells with PP2, a selective Src kinase inhibitor, led to inhibition of E4orf4-dependent membrane blebbing and later to a marked decrease in E4orf4-induced nuclear condensation. Taken together, these observations indicate that expression of adenovirus 2 E4orf4 can initiate caspase-independent extranuclear manifestations of apoptosis through a modulation of Src family kinases and that these are involved in signaling E4orf4-dependent apoptosis. This study also suggests that Src family kinases are likely to play a role in the cytoplasmic execution of apoptotic programs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.