ArticleThe Journal of cell biology2002
Distinct cell death pathways triggered by the adenovirus early region 4 ORF 4 protein.
Article in The Journal of cell biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 53 citations in OpenAlex.
- Adenoviral protein E4orf4 interacts with the polarity protein Par3 to induce nuclear rupture and tumor cell death.The Journal of cell biology · 2020Article
- Cancer Treatment Goes Viral: Using Viral Proteins to Induce Tumour-Specific Cell Death.Cancers · 2019Review
- Characterization of a replicating expanded tropism oncolytic reovirus carrying the adenovirus E4orf4 gene.Gene therapy · 2018Article
- 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
- Control the host cell cycle: viral regulation of the anaphase-promoting complex.Journal of virology · 2013Review
- 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
- The adenovirus E4orf4 protein targets PP2A to the ACF chromatin-remodeling factor and induces cell death through regulation of SNF2h-containing complexes.Nucleic acids research · 2011Article
- Genetic analysis of B55alpha/Cdc55 protein phosphatase 2A subunits: association with the adenovirus E4orf4 protein.Journal of virology · 2011Article
- Viral takeover of the host ubiquitin system.Frontiers in microbiology · 2011Article
- Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells.The Journal of cell biology · 2010Article
- The cytosolic tail of the Golgi apyrase Ynd1 mediates E4orf4-induced toxicity in Saccharomyces cerevisiae.PloS one · 2010Article
- Regulation of cell death by recycling endosomes and golgi membrane dynamics via a pathway involving Src-family kinases, Cdc42 and Rab11a.Molecular biology of the cell · 2009Article
- The adenovirus E4orf4 protein induces G2/M arrest and cell death by blocking protein phosphatase 2A activity regulated by the B55 subunit.Journal of virology · 2009Article
- Localization and importance of the adenovirus E4orf4 protein during lytic infection.Journal of virology · 2009Article
- The adenovirus E4orf4 protein induces growth arrest and mitotic catastrophe in H1299 human lung carcinoma cells.Oncogene · 2009Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In transformed cells, induction of apoptosis by adenovirus type 2 (Ad2) early region 4 ORF 4 (E4orf4) correlates with accumulation of E4orf4 in the cell membrane-cytoskeleton fraction. However, E4orf4 is largely expressed in nuclear regions before the onset of apoptosis. To determine the relative contribution of nuclear E4orf4 versus membrane-associated E4orf4 to cell death signaling, we engineered green fluorescent fusion proteins to target E4orf4 to specific cell compartments. The targeting of Ad2 E4orf4 to cell membranes through a CAAX-box or a myristylation consensus signal sufficed to mimic the fast Src-dependent apoptotic program induced by wild-type E4orf4. In marked contrast, the nuclear targeting of E4orf4 abolished the early induction of extranuclear apoptosis. However, nuclear E4orf4 still induced a delayed cell death response independent of Src-like activity and of E4orf4 tyrosine phosphorylation. The zVAD.fmk-inhibitable caspases were dispensable for execution of both cell death programs. Nevertheless, both pathways led to caspase activation in some cell types through the mitochondrial pathway. Finally, our data support a critical role for calpains upstream in the death effector pathway triggered by the Src-mediated cytoplasmic death signal. We conclude that Ad2 E4orf4 induces two distinct cell death responses, whose relative contributions to cell killing may be determined by the genetic background.
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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.