Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding H P, Ron D
Skirball Institute of Biomolecular Medicine, Departments of Medicine, Cell Biology and the Kaplan Cancer Center, New York University Medical School, New York, NY 10016, USA.
Science. 2000 Jan 28;287(5453):664-6. doi: 10.1126/science.287.5453.664.
Malfolded proteins in the endoplasmic reticulum (ER) induce cellular stress and activate c-Jun amino-terminal kinases (JNKs or SAPKs). Mammalian homologs of yeast IRE1, which activate chaperone genes in response to ER stress, also activated JNK, and IRE1alpha-/- fibroblasts were impaired in JNK activation by ER stress. The cytoplasmic part of IRE1 bound TRAF2, an adaptor protein that couples plasma membrane receptors to JNK activation. Dominant-negative TRAF2 inhibited activation of JNK by IRE1. Activation of JNK by endogenous signals initiated in the ER proceeds by a pathway similar to that initiated by cell surface receptors in response to extracellular signals.
内质网（ER）中错误折叠的蛋白质会引发细胞应激并激活c-Jun氨基末端激酶（JNKs或SAPKs）。酵母IRE1的哺乳动物同源物可响应内质网应激激活伴侣蛋白基因，它也能激活JNK，并且IRE1α-/-成纤维细胞在内质网应激激活JNK的过程中存在缺陷。IRE1的胞质部分与TRAF2结合，TRAF2是一种衔接蛋白，可将质膜受体与JNK激活相偶联。显性负性TRAF2抑制IRE1对JNK的激活。在内质网中由内源性信号引发的JNK激活过程，其途径类似于细胞表面受体响应细胞外信号所引发的途径。
