ArticleJournal of virology2003
E1A sensitizes cells to tumor necrosis factor alpha by downregulating c-FLIP S.
Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 66 citations in OpenAlex.
- A new perspective of triptolide-associated hepatotoxicity: the relevance of NF-Acta pharmaceutica Sinica. B · 2020Article
- Cancer Treatment Goes Viral: Using Viral Proteins to Induce Tumour-Specific Cell Death.Cancers · 2019Review
- Article
- Tumor suppressor BLU promotes TRAIL-induced apoptosis by downregulating NF-κB signaling in nasopharyngeal carcinoma.Oncotarget · 2017Article
- Article
- Herpes simplex virus type 1 (HSV-1)-induced apoptosis in human dendritic cells as a result of downregulation of cellular FLICE-inhibitory protein and reduced expression of HSV-1 antiapoptotic latency-associated transcript sequences.Journal of virology · 2010Article
- A TNF- and c-Cbl-dependent FLIP(S)-degradation pathway and its function in Mycobacterium tuberculosis-induced macrophage apoptosis.Nature immunology · 2009Article
- Macrophage migration inhibitory factor governs endothelial cell sensitivity to LPS-induced apoptosis.American journal of respiratory cell and molecular biology · 2008Article
- The Fas death signaling pathway connecting reactive oxygen species generation and FLICE inhibitory protein down-regulation.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- mTOR-independent translational control of the extrinsic cell death pathway by RalA.Molecular and cellular biology · 2006Article
- Hepatitis C virus core protein inhibits tumor necrosis factor alpha-mediated apoptosis by a protective effect involving cellular FLICE inhibitory protein.Journal of virology · 2006Article
- Modulation of tumor necrosis factor by microbial pathogens.PLoS pathogens · 2006Review
- Viruses - seeking and destroying the tumor program.Oncogene · 2005Review
- mTOR controls FLIPS translation and TRAIL sensitivity in glioblastoma multiforme cells.Molecular and cellular biology · 2005Article
- The androgen receptor directly targets the cellular Fas/FasL-associated death domain protein-like inhibitory protein gene to promote the androgen-independent growth of prostate cancer cells.Molecular endocrinology (Baltimore, Md.) · 2005Article
- Macrophages kill human papillomavirus type 16 E6-expressing tumor cells by tumor necrosis factor alpha- and nitric oxide-dependent mechanisms.Journal of virology · 2005Article
- Hypoxia and defective apoptosis drive genomic instability and tumorigenesis.Genes & development · 2004Article
- E1A and E1B proteins inhibit inflammation induced by adenovirus.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis.Oncogene · 2003Review
- Cellular FLICE-inhibitory protein: an attractive therapeutic target?Expert opinion on therapeutic targets · 2003Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor necrosis factor alpha (TNF-alpha) activates both apoptosis and NF-kappaB-dependent survival pathways, the former of which requires inhibition of gene expression to be manifested. c-FLIP is a TNF-alpha-induced gene that inhibits caspase-8 activation during TNF-alpha signaling. Adenovirus infection and E1A expression sensitize cells to TNF-alpha by allowing apoptosis in the absence of inhibitors of gene expression, suggesting that it may be disabling a survival signaling pathway. E1A promoted TNF-alpha-mediated activation of caspase-8, suggesting that sensitivity was occurring at the level of the death-inducing signaling complex. Furthermore, E1A expression downregulated c-FLIP(S) expression and prevented its induction by TNF-alpha. c-FLIP(S) and viral FLIP expression rescued E1A-mediated sensitization to TNF-alpha by restoring the resistance of caspase-8 to activation, thereby preventing cell death. E1A inhibited TNF-alpha-dependent induction of c-FLIP(S) mRNA and stimulated ubiquitination- and proteasome-dependent degradation of c-FLIP(S) protein. Since elevated c-FLIP levels confer resistance to apoptosis and promote tumorigenicity, interference with its induction by NF-kappaB and stimulation of its destruction in the proteasome may provide novel therapeutic approaches for facilitating the elimination of apoptosis-refractory tumor cells.
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Registered trials
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.