Letter abstract
Nature Cell Biology 7, 186 - 194 (2005)
Published online: 23 January 2005 | doi:10.1038/ncb1213
OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes
Shinichi Kondo1,2, Tomohiko Murakami1,2, Kouko Tatsumi3, Maiko Ogata1,2, Soshi Kanemoto1,2, Kumi Otori2, Ken Iseki4, Akio Wanaka3 & Kazunori Imaizumi1
Endoplasmic reticulum (ER) stress transducers IRE1, PERK and ATF6 are well known to transduce signals from the ER to the cytoplasm and nucleus when unfolded proteins are accumulated in the ER. Here, we identified OASIS as a novel ER stress transducer. OASIS is a basic leucine zipper (bZIP) transcription factor of the CREB/ATF family with a transmembrane domain that allows it to associate with the ER. The molecule is cleaved at the membrane in response to ER stress, and its cleaved amino-terminal cytoplasmic domain, which contains the bZIP domain, translocates into the nucleus where it activates the transcription of target genes that are mediated by ER stress-responsive and cyclic AMP-responsive elements. Intriguingly, OASIS was induced at the transcriptional level during ER stress in astrocytes of the central nervous system, but not in other cell types examined. Furthermore, overexpression of OASIS resulted in induction of BiP and suppression of ER-stress-induced cell death, whereas knockdown partially reduced BiP levels and led to ER stress in susceptible astrocytes. Our results reveal pivotal roles for OASIS in modulating the unfolded protein response in astrocytes, and the possibility that cell type-specific UPR signalling also exists in other cells.
- Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki 889-1692, Japan.
- Division of Structural Cellular Biology, Nara Institute of Science and Technology (NAIST), 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.
- Department of Anatomy, Nara Medical University, 840 Shijyo-cho, Kashihara, Nara 634-8522, Japan.
- Department of Emergency Medicine, Yamagata University, School of Medicine, 2-2-2 Iidanishi Yamagata city, Yamagata 990-9585, Japan.
Correspondence to: Kazunori Imaizumi1 e-mail: imaizumi@med.miyazaki-u.ac.jp
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