TY - JOUR
T1 - Recruitment of tumor necrosis factor receptor-associated factor family proteins to apoptosis signal-regulating kinase 1 signalosome is essential for oxidative stress-induced cell death
AU - Noguchi, Takuya
AU - Takeda, Kohsuke
AU - Matsuzawa, Atsushi
AU - Saegusa, Kaoru
AU - Nakano, Hiroyasu
AU - Gohda, Jin
AU - Inoue, Jun Ichiro
AU - Ichijo, Hidenori
PY - 2005/11/4
Y1 - 2005/11/4
N2 - Apoptosis signal-regulating kinase 1 (ASK1) plays a pivotal role in oxidative stress-induced cell death. Reactive oxygen species disrupt the interaction of ASK1 with its cellular inhibitor thioredoxin and thereby activates ASK1. However, the precise mechanism by which ASK1 freed from thioredoxin undergoes oligomerization-dependent activation has not been fully elucidated. Here we show that endogenous ASK1 constitutively forms a high molecular mass complex including Trx (∼1,500-2,000 kDa), which we designate ASK1 signalosome. Upon H2O2 treatment, the ASK1 signalosome forms a higher molecular mass complex at least in part because of the recruitment of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF6. Consistent with our previous findings that TRAF2 and TRAF6 activate ASK1, H2O2-induced ASK1 activation and cell death were strongly reduced in the cells derived from Traf2-/- and Traf6-/- mice. A novel signaling complex including TRAF2, TRAF6, and ASK1 may thus be the key component in oxidative stress-induced cell death.
AB - Apoptosis signal-regulating kinase 1 (ASK1) plays a pivotal role in oxidative stress-induced cell death. Reactive oxygen species disrupt the interaction of ASK1 with its cellular inhibitor thioredoxin and thereby activates ASK1. However, the precise mechanism by which ASK1 freed from thioredoxin undergoes oligomerization-dependent activation has not been fully elucidated. Here we show that endogenous ASK1 constitutively forms a high molecular mass complex including Trx (∼1,500-2,000 kDa), which we designate ASK1 signalosome. Upon H2O2 treatment, the ASK1 signalosome forms a higher molecular mass complex at least in part because of the recruitment of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF6. Consistent with our previous findings that TRAF2 and TRAF6 activate ASK1, H2O2-induced ASK1 activation and cell death were strongly reduced in the cells derived from Traf2-/- and Traf6-/- mice. A novel signaling complex including TRAF2, TRAF6, and ASK1 may thus be the key component in oxidative stress-induced cell death.
UR - http://www.scopus.com/inward/record.url?scp=27744559915&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27744559915&partnerID=8YFLogxK
U2 - 10.1074/jbc.M506771200
DO - 10.1074/jbc.M506771200
M3 - Article
C2 - 16129676
AN - SCOPUS:27744559915
VL - 280
SP - 37033
EP - 37040
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 44
ER -