Journal article
Stress-induced decrease in TRAF2 stability is mediated by Siah2
The EMBO journal, Vol.21(21), pp.5756-5765
11/01/2002
DOI: 10.1093/emboj/cdf576
PMCID: PMC131073
PMID: 12411493
Abstract
TRAF2 serves as a central regulator of the cellular response to stress and cytokines through the regulation of key stress-signaling cascades. Here we demonstrate that wild-type, but not RING mutant, Siah2 targets TRAF2 for ubiquitylation and degradation
in vitro
. Siah2 mediates equally efficient ubiquitylation of RING mutant TRAF2.
In vivo
, Siah2 primarily targets TRAF2 for degradation under stress conditions. Tumor necrosis factor-α (TNF-α) and actinomycin D treatment results in accelerated TRAF2 degradation in wild-type mouse embryo fibroblasts (MEFs), as compared with
Siah2
–/–
cells. Similarly, TRAF2 half-life is prolonged in
Siah2
–/–
compared with wild-type MEFs subjected to stress stimuli. Siah2 efficiently decreases TNF-α-dependent induction of JNK activity and transcriptional activation of NF-κB. Apoptosis induced by TNF-α and actinomycin D treatment is increased upon expression of Siah2, or attenuated upon expression of TRAF2 or RING mutant Siah2. Identifying Siah2 as a regulator of TRAF2 stability reveals its role in the regulation of TRAF2 signaling following exposure to stress.
Details
- Title: Subtitle
- Stress-induced decrease in TRAF2 stability is mediated by Siah2
- Creators
- Hasem Habelhah - Ruttenberg Cancer Center andIan J Frew - Ruttenberg Cancer Center andAaron Laine - Ruttenberg Cancer Center andPeter W Janes - Ruttenberg Cancer Center andFrederic Relaix - Ruttenberg Cancer Center andDavid Sassoon - Ruttenberg Cancer Center andDavid D.L Bowtell - Ruttenberg Cancer Center andZe’ev Ronai - Ruttenberg Cancer Center and
- Resource Type
- Journal article
- Publication Details
- The EMBO journal, Vol.21(21), pp.5756-5765
- Publisher
- Oxford University Press; Oxford, UK
- DOI
- 10.1093/emboj/cdf576
- PMID
- 12411493
- PMCID
- PMC131073
- ISSN
- 0261-4189
- eISSN
- 1460-2075
- Language
- English
- Date published
- 11/01/2002
- Academic Unit
- Pathology
- Record Identifier
- 9984047653602771
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