The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Induction of gadd45β by NF-κB downregulates pro-apoptotic JNK signalling
Abstract
In addition to coordinating immune and inflammatory responses, NF-kappaB/Rel transcription factors control cell survival. Normally, NF-kappaB dimers are sequestered in the cytoplasm by binding to inhibitory IkappaB proteins, and can be activated rapidly by signals that induce the sequential phosphorylation and proteolysis of IkappaBs. Activation of NF-kappaB antagonizes apoptosis or programmed cell death by numerous triggers, including the ligand engagement of 'death receptors' such as tumour-necrosis factor (TNF) receptor. The anti-apoptotic activity of NF-kappaB is also crucial to oncogenesis and to chemo- and radio-resistance in cancer. Cytoprotection by NF-kappaB involves the activation of pro-survival genes; however, its basis remains poorly understood. Here we report that NF-kappaB complexes downregulate the c-Jun amino-terminal kinase (JNK) cascade, thus establishing a link between the NF-kappaB and the JNK pathways. This link involves the transcriptional upregulation of gadd45beta/myd118 (ref. 4), which downregulates JNK signalling induced by the TNF receptor (TNF-R). This NF-kappaB-dependent inhibition of the JNK pathway is central to the control of cell death. Our findings define a protective mechanism that is mediated by NF-kappaB complexes and establish a role for the persistent activation of JNK in the apoptotic response to TNF-alpha.
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“However, in the absence of NF-κB, this JNK activation is greatly extended, allowing for increased cell death 57, 58.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [58]
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Metadata
- Authors
- De Smaele, E., Zazzeroni, F., Papa, S., Nguyen, D. U., Jin, R., Jones, J., Cong, R., & Franzoso, G.
- Affiliations
- University of Chicago (US)
- Corresponding author
- Franzoso, Guido
- Venue
- Nature
- Published
- 2001-11
- Volume
- 414
- Issue
- 6861
- Pages
- 308-313
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1563090311
- Cited by
- 732
- References
- 30
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 14 · 2023: 11 · 2022: 12 · 2021: 16 · 2020: 10 · 2019: 16 · 2018: 24 · 2017: 12 · 2016: 25 · 2015: 16 · 2014: 18 · 2013: 29 · 2012: 22
- FWCI
- 22.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- NF-κB, GADD45B, JNK signaling, apoptosis, TNF receptor, TNF-α, cell survival, transcriptional regulation, IκB, death receptors, anti-apoptotic signaling
- MeSH terms
- GADD45 Proteins, Animals, Antigens, Differentiation, Cell Line, Cell Survival, Cycloheximide, Gene Expression Regulation, Protein Synthesis Inhibitors, Tumor Necrosis Factor-alpha, NF-kappa B, 3T3 Cells, Apoptosis, Receptors, Tumor Necrosis Factor, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, JNK Mitogen-Activated Protein Kinases, Mice
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