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Publication : OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes.

First Author  Kondo S Year  2005
Journal  Nat Cell Biol Volume  7
Issue  2 Pages  186-94
PubMed ID  15665855 Mgi Jnum  J:217998
Mgi Id  MGI:5616321 Doi  10.1038/ncb1213
Citation  Kondo S, et al. (2005) OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes. Nat Cell Biol 7(2):186-94
abstractText  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.
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