PMID- 12843613 OWN - NLM STAT- MEDLINE DCOM- 20040304 LR - 20211203 IS - 0918-6158 (Print) IS - 0918-6158 (Linking) VI - 26 IP - 7 DP - 2003 Jul TI - Activation signal of nuclear factor-kappa B in response to endoplasmic reticulum stress is transduced via IRE1 and tumor necrosis factor receptor-associated factor 2. PG - 931-5 AB - Conditions that perturb the function of the endoplasmic reticulum (ER) lead to an accumulation of proteins and subsequent induction of several responses, such as an increased expression of ER-resident chaperones involved in protein folding and activation of c-jun N-terminal kinase (JNK). These responses are mediated by a transmembrane kinase/ribonuclease, IRE1, which transduces the signal from the ER lumen to the cytosol. Although nuclear transcription factor-kappaB (NF-kappaB) is also activated by ER stress, whether this response depends on IRE1 is unknown. In this study, we show that IRE1 is involved in the activation of NF-kappaB induced by ER stress. NF-kappaB was activated by ER stress-inducing agents, thapsigargin and tunicamycin. The activation was inhibited by a dominant-negative IRE1. In addition, a dominant-negative TRAF2 also suppressed the activation of NF-kappaB by ER stress. These results suggest that ER stress-induced NF-kappaB activation is also mediated by the IRE1-TRAF2 pathway, as well as JNK activation. FAU - Kaneko, Masayuki AU - Kaneko M AD - Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. FAU - Niinuma, Yoshifumi AU - Niinuma Y FAU - Nomura, Yasuyuki AU - Nomura Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - 0 (Membrane Proteins) RN - 0 (NF-kappa B) RN - 0 (Proteins) RN - 0 (TNF Receptor-Associated Factor 2) RN - 67526-95-8 (Thapsigargin) RN - EC 2.7.1.- (ERN2 protein, human) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 3.1.- (Endoribonucleases) SB - IM MH - Cell Line MH - Endoplasmic Reticulum/drug effects/genetics/*metabolism MH - Endoribonucleases MH - Humans MH - Membrane Proteins/genetics/*metabolism MH - NF-kappa B/genetics/*metabolism MH - Protein Serine-Threonine Kinases/genetics/*metabolism MH - Proteins/genetics/*metabolism MH - Signal Transduction/drug effects/*physiology MH - TNF Receptor-Associated Factor 2 MH - Thapsigargin/toxicity EDAT- 2003/07/05 05:00 MHDA- 2004/03/05 05:00 CRDT- 2003/07/05 05:00 PHST- 2003/07/05 05:00 [pubmed] PHST- 2004/03/05 05:00 [medline] PHST- 2003/07/05 05:00 [entrez] AID - 10.1248/bpb.26.931 [doi] PST - ppublish SO - Biol Pharm Bull. 2003 Jul;26(7):931-5. doi: 10.1248/bpb.26.931.