Journal article
Ubiquitination and translocation of TRAF2 is required for activation of JNK but not of p38 or NF-κB
The EMBO journal, Vol.23(2), pp.322-332
01/28/2004
DOI: 10.1038/sj.emboj.7600044
PMCID: PMC1271753
PMID: 14713952
Abstract
TRAF2 is a RING finger protein that regulates the cellular response to stress and cytokines by controlling JNK, p38 and NF-κB signaling cascades. Here, we demonstrate that TRAF2 ubiquitination is required for TNFα-induced activation of JNK but not of p38 or NF-κB. Intact RING and zinc finger domains are required for TNFα-induced TRAF2 ubiquitination, which is also dependent on Ubc13. TRAF2 ubiquitination coincides with its translocation to the insoluble cellular fraction, resulting in selective activation of JNK. Inhibition of Ubc13 expression by RNAi resulted in inhibition of TNFα-induced TRAF2 translocation and impaired activation of JNK but not of IKK or p38. TRAF2 aggregates in the cytoplasm, as seen in Hodgkin–Reed–Sternberg lymphoma cells, resulting in constitutive NF-κB activity but failure to activate JNK. These findings demonstrate that the TRAF2 RING is required for Ubc13-dependent ubiquitination, resulting in translocation of TRAF2 to an insoluble fraction and activation of JNK, but not of p38 or NF-κB. Altogether, our findings highlight a novel mechanism of TRAF2-dependent activation of diverse signaling cascades that is impaired in Hodgkin–Reed–Sternberg cells.
Details
- Title: Subtitle
- Ubiquitination and translocation of TRAF2 is required for activation of JNK but not of p38 or NF-κB
- Creators
- Hasem Habelhah - Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY, USAShoichi Takahashi - Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY, USASsang-Goo Cho - Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY, USATakayuki Kadoya - Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY, USAToshiki Watanabe - Department of Cancer Research, The Institute of Medical Science, The University of Tokyo, Tokyo, JapanZe'ev Ronai - Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY, USA
- Resource Type
- Journal article
- Publication Details
- The EMBO journal, Vol.23(2), pp.322-332
- DOI
- 10.1038/sj.emboj.7600044
- PMID
- 14713952
- PMCID
- PMC1271753
- ISSN
- 0261-4189
- eISSN
- 1460-2075
- Alternative title
- TNFα-induced TRAF2 Ub activates JNK but not IKK
- Language
- English
- Date published
- 01/28/2004
- Academic Unit
- Pathology
- Record Identifier
- 9984047695902771
Metrics
18 Record Views