ArticleMolecular and cellular biology2004
Sustained activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase pathways by hepatitis B virus X protein mediates apoptosis via induction of Fas/FasL and tumor necrosis factor (TNF) receptor 1/TNF-alpha expression.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 87 citations in OpenAlex.
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- Microbiome in human cancers.Access microbiology · 2021Review
- Suppression of Interferon-α Treatment Response by Host Negative Factors in Hepatitis B Virus Infection.Frontiers in medicine · 2021Review
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- X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy.Virus research · 2017Article
- Interference of Apoptosis by Hepatitis B Virus.Viruses · 2017Review
- Alpha-mangostin induces apoptosis through activation of reactive oxygen species and ASK1/p38 signaling pathway in cervical cancer cells.Oncotarget · 2017Article
- Blocking two-component signalling enhances Candida albicans virulence and reveals adaptive mechanisms that counteract sustained SAPK activation.PLoS pathogens · 2017Article
- Quercetin-3-Biomolecules & therapeutics · 2016Article
- JNK and p38 mitogen-activated protein kinase pathways contribute to porcine epidemic diarrhea virus infection.Virus research · 2016Article
- The alkyllysophospholipid edelfosine enhances TRAIL-mediated apoptosis in gastric cancer cells through death receptor 5 and the mitochondrial pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Hepatitis B Virus X and Regulation of Viral Gene Expression.Cold Spring Harbor perspectives in medicine · 2016Review
- Hepatitis B virus molecular biology and pathogenesis.Hepatoma research · 2016Article
- Hepatitis B and C virus-induced hepatitis: Apoptosis, autophagy, and unfolded protein response.World journal of gastroenterology · 2015Article
- F-box only protein 31 (FBXO31) negatively regulates p38 mitogen-activated protein kinase (MAPK) signaling by mediating lysine 48-linked ubiquitination and degradation of mitogen-activated protein kinase kinase 6 (MKK6).The Journal of biological chemistry · 2014Article
- N-(p-Coumaryol)-Tryptamine Suppresses the Activation of JNK/c-Jun Signaling Pathway in LPS-Challenged RAW264.7 Cells.Biomolecules & therapeutics · 2014Article
- Anti-tumor pharmacological evaluation of extracts from stellera chamaejasme L based on hollow fiber assay.BMC complementary and alternative medicine · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Activation of the cellular stress pathways (c-Jun N-terminal kinase [JNK] and p38 mitogen-activated protein [MAP] kinase) is linked to apoptosis. However, whether both pathways are required for apoptosis remains unresolved. Hepatitis B virus X protein (pX) activates p38 MAP kinase and JNK pathways and, in response to weak apoptotic signals, sensitizes hepatocytes to apoptosis. Employing hepatocyte cell lines expressing pX, which was regulated by tetracycline, we investigated the mechanism of apoptosis by p38 MAP kinase and JNK pathway activation. Inhibition of the p38 MAP kinase pathway rescues by 80% the initiation of pX-mediated apoptosis, whereas subsequent apoptotic events involve both pathways. pX-mediated activation of p38 MAP kinase and JNK pathways is sustained, inducing the transcription of the death receptor family genes encoding Fas/FasL and tumor necrosis factor receptor 1 (TNFR1)/TNF-alpha and the p53-regulated Bax and Noxa genes. The pX-dependent expression of Fas/FasL and TNFR1/TNF-alpha mediates caspase 8 activation, resulting in Bid cleavage. In turn, activated Bid, acting with pX-induced Bax and Noxa, mediates the mitochondrial release of cytochrome c, resulting in the activation of caspase 9 and apoptosis. Combined antibody neutralization of FasL and TNF-alpha reduces by 70% the initiation of pX-mediated apoptosis. These results support the importance of the pX-dependent activation of both the p38 MAP kinase and JNK pathways in pX-mediated apoptosis and suggest that this mechanism of apoptosis occurs in vivo in response to weak apoptotic signals.
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