PMID- 12411493
OWN - NLM
STAT- MEDLINE
DCOM- 20021210
LR  - 20190607
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 21
IP  - 21
DP  - 2002 Nov 1
TI  - Stress-induced decrease in TRAF2 stability is mediated by Siah2.
PG  - 5756-65
AB  - 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-alpha (TNF-alpha) 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-alpha-dependent induction of 
      JNK activity and transcriptional activation of NF-kappaB. Apoptosis induced by 
      TNF-alpha 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.
FAU - Habelhah, Hasem
AU  - Habelhah H
AD  - Ruttenberg Cancer Center and Department of Biochemistry and Molecular Biology, 
      Mount Sinai School of Medicine, New York, NY 10029, USA.
FAU - Frew, Ian J
AU  - Frew IJ
FAU - Laine, Aaron
AU  - Laine A
FAU - Janes, Peter W
AU  - Janes PW
FAU - Relaix, Frederic
AU  - Relaix F
FAU - Sassoon, David
AU  - Sassoon D
FAU - Bowtell, David D L
AU  - Bowtell DD
FAU - Ronai, Ze'ev
AU  - Ronai Z
LA  - eng
GR  - CA77389/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteins)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Ubiquitin)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (seven in absentia proteins)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism
MH  - Nuclear Proteins/*physiology
MH  - *Oxidative Stress
MH  - Proteins/genetics/*metabolism
MH  - Signal Transduction
MH  - TNF Receptor-Associated Factor 2
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Ubiquitin/metabolism
MH  - Ubiquitin-Protein Ligases
MH  - Ultraviolet Rays
PMC - PMC131073
EDAT- 2002/11/02 04:00
MHDA- 2002/12/11 04:00
PMCR- 2003/11/01
CRDT- 2002/11/02 04:00
PHST- 2002/11/02 04:00 [pubmed]
PHST- 2002/12/11 04:00 [medline]
PHST- 2002/11/02 04:00 [entrez]
PHST- 2003/11/01 00:00 [pmc-release]
AID - cdf576 [pii]
AID - 10.1093/emboj/cdf576 [doi]
PST - ppublish
SO  - EMBO J. 2002 Nov 1;21(21):5756-65. doi: 10.1093/emboj/cdf576.