Tumour necrosis factor receptor 1 mediates endoplasmic reticulum stress-induced activation of the MAP kinase JNK.

Tumour necrosis factor receptor (TNFR)1 is the main receptor responsible for TNF-induced diverse cellular events. In this study, we report that TNFR1 has a crucial role in endoplasmic reticulum (ER) stress-induced Jun amino-terminal kinase (JNK) activation. Although ER stress leads to JNK activation in wild-type mouse embryo fibroblasts, we failed to detect any JNK activation in TNFR1-/- cells. ER stress-induced JNK activation is restored in TNFR1-/- cells when TNFR1 expression is reconstituted. We also found that TNFR1 functions downstream of IRE1 and that IRE1 is present in the same complex with TNFR1 under ER stress condition. Therefore, our study shows a novel role of TNFR1 in mediating ER stress-induced JNK activation.