Activation Signal of Nuclear Factor-κB in Response to Endoplasmic Reticulum Stress is Transduced via IRE1 and Tumor Necrosis Factor Receptor-Associated Factor 2

Kaneko Masayuki

Niinuma Yoshifumi

Nomura Yasuyuki

Biological and Pharmaceutical Bulletin

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-κB (NF-κB) 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-κB induced by ER stress. NF-κB 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-κB by ER stress. These results suggest that ER stress-induced NF-κB activation is also mediated by the IRE1-TRAF2 pathway, as well as JNK activation.

endoplasmic reticulum (ER) stress

nuclear transcription factor-κB (NF-κB)

IRE1

TRAF2

Medical sciences [ 490 ]

eng

The Pharmaceutical Society of Japan

© 2003 Pharmaceutical Society of Japan

[ISSN] 0918-6158

[ISSN] 1347-5215

[NCID] AA10885497

[DOI] 10.1248/bpb.26.931

[DOI] https://doi.org/10.1248/bpb.26.931