OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes.
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.
Kondo
Shinichi
S
Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki 889-1692, Japan.
Murakami
Tomohiko
T
Tatsumi
Kouko
K
Ogata
Maiko
M
Kanemoto
Soshi
S
Otori
Kumi
K
Iseki
Ken
K
Wanaka
Akio
A
Imaizumi
Kazunori
K
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D009154:Mutation; D017510:Protein Folding; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D000091342:Endoplasmic Reticulum Chaperone BiP
D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP