Journal article
TRAF2 phosphorylation promotes NF-κB–dependent gene expression and inhibits oxidative stress-induced cell death
Molecular biology of the cell, Vol.22(1), pp.128-140
01/2011
DOI: 10.1091/mbc.e10-06-0556
PMCID: PMC3016971
PMID: 21119000
Abstract
Tumor necrosis factor α (TNF-α) receptor–associated factor 2 (TRAF2) regulates activation of the c-Jun N-terminal kinase (JNK)/c-Jun and the inhibitor of κB kinase (IKK)/nuclear factor κB (NF-κB) signaling cascades in response to TNF-α stimulation. Gene knockout studies have revealed that TRAF2 inhibits TNF-α–induced cell death but promotes oxidative stress–induced apoptosis. Here we report that TNF-α and oxidative stress both induce TRAF2 phosphorylation at serines 11 and 55 and that this dual phosphorylation promotes the prolonged phase of IKK activation while inhibiting the prolonged phase of JNK activation. Prolonged IKK activation trigged by TNF-α plays an essential role in efficient expression of a subset of NF-κB target genes but has no substantial role in TNF-α–induced cell death. On the other hand, TRAF2 phosphorylation in response to oxidative stress significantly promotes cell survival by inducing prolonged IKK activation and by inhibiting the prolonged phase of JNK activation. Notably, stable expression of phospho-null mutant TRAF2 in cancer cells leads to an increase in the basal and inducible JNK activation and B-cell lymphoma 2 (Bcl-2) phosphorylation. In addition, exposure of cells expressing phospho-null mutant TRAF2 to sublethal oxidative stress results in a rapid degradation of Bcl-2 and cellular inhibitor of apoptosis 1 as well as significantly increased cell death. These results suggest that TRAF2 phosphorylation is essential for cell survival under conditions of oxidative stress.
Details
- Title: Subtitle
- TRAF2 phosphorylation promotes NF-κB–dependent gene expression and inhibits oxidative stress-induced cell death
- Creators
- Laiqun Zhang - Department of Pathology, Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242Ken Blackwell - Department of Pathology, Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242Aliya Altaeva - Department of Pathology, Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242Zhaohui Shi - Department of Pathology, Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242Hasem Habelhah - Department of Pathology, Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242
- Contributors
- Kunxin Luo (Editor) - University of California, Berkeley
- Resource Type
- Journal article
- Publication Details
- Molecular biology of the cell, Vol.22(1), pp.128-140
- DOI
- 10.1091/mbc.e10-06-0556
- PMID
- 21119000
- PMCID
- PMC3016971
- NLM abbreviation
- Mol Biol Cell
- ISSN
- 1059-1524
- eISSN
- 1939-4586
- Publisher
- American Society for Cell Biology
- Language
- English
- Date published
- 01/2011
- Academic Unit
- Pathology
- Record Identifier
- 9984046912802771
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