Cell Death and Differentiation (2002) 9, 1108 ± 1114 ã 2002 Nature Publishing Group All rights reserved 1350-9047/02 $25.00 www.nature.com/cdd Caspase-12 processing and fragment translocation into nuclei of tunicamycin-treated cells E Fujita1,4, Y Kouroku1,4, A Jimbo1, A Isoai2, K Maruyama3 proteins called IREs1 that lead to the induction of ER stress. and T Momoi*,1 For instance, IRE1-a mediates ER stress signals induced by agents such as tunicamycin, which blocks N-linked protein 2 1 Divisions of Development and Differentiation, National Institute of glycosylation in the ER. Upon activation, IRE1-a can recruit Neuroscience, NCNP, Kodaira, Tokyo, Japan the cytosolic adaptor protein, TNF receptor-associated factor 2 Asahi glass Co., Hasawa-cho, Kanagawa-ku, Yokohama, Kanagawa, Japan 2 (TRAF2), which in turn recruits and activates the proximal 3 Department of Pharmacology, Saitama Medical School, Moroyama, Saitama, components of the c-Jun N-terminal kinase (JNK) pathway. Japan 4 ER stress also leads to the activation of genes possessing a The ®rst two authors contributed equally to this work. 3 * Corresponding author: T Momoi, Division of Development and Differentiation, UPR element in the promoter region. Such genes include the National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, Japan. Bip/Grp78 protein that increases protein folding in the ER Tel: +81-42-341-2711 Ext 5273; Fax: +81-42-346-1754; lumen. When these stress signals are unable to rescue cells, E-mail:
[email protected] the apoptotic pathway is activated. However, little is known about the molecular mechanism of cell death induced by ER Received 23.1.02; revised 10.5.02; accepted 13.5.02 stress.