Author/Authors :
Xiaohua Shen، نويسنده , , Ronald E. Ellis، نويسنده , , Kyungho Lee، نويسنده , , Chuan-Yin Liu، نويسنده , , Kun Yang، نويسنده , , Aaron Solomon، نويسنده , , Hiderou Yoshida، نويسنده , , Rick Morimoto، نويسنده , , David M. Kurnit، نويسنده , , Kazutoshi Mori، نويسنده , , Randal J. Kaufman، نويسنده ,
Abstract :
The unfolded protein response (UPR) is a transcriptional and translational intracellular signaling pathway activated by the accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER). We have used C. elegans as a genetic model system to dissect UPR signaling in a multicellular organism. C. elegans requires ire-1-mediated splicing of xbp-1 mRNA for UPR gene transcription and survival upon ER stress. In addition, ire-1/xbp-1 acts with pek-1, a protein kinase that mediates translation attenuation, in complementary pathways that are essential for worm development and survival. We propose that UPR transcriptional activation by ire-1 as well as translational attenuation by pek-1 maintain ER homeostasis. The results demonstrate that the UPR and ER homeostasis are essential for metazoan development.
