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

Abstract

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.

Analysis of ATF6 Activation in Site-2 Protease-deficient Chinese Hamster Ovary Cells

“…Because other UPR regulators controlled by mammalian Rip exhibit tissue-specific expression, e.g. OASIS in astrocytes (Kondo et al, 2005) and CREB-H in liver (Zhang et al, 2006), these results strongly suggest that ATF6 is indispensable to the induction of ER chaperones in response to ER stress. Furthermore, even if they were expressed in CHO cells, their contribution to the ERSE-mediated induction of ER chaperones would be marginal because CREB-H enhances UPR element-mediated transcription but not ERSE-mediated transcription (Zhang et al, 2006) and because OASIS prefers cAMP-response element to ERSE (Kondo et al, 2005).…”

“…SREBPs with a hairpin structure are responsible for cholesterol homeostasis . On the other hand, transmembrane proteins with type II topology, such as ATF6, OASIS (Kondo et al, 2005), and CREB-H (Zhang et al, 2006), are involved in the UPR where they maintain the homeostasis of the ER. Interestingly, these ER membrane-bound transcription factors are cleaved by the same two proteases localized in the Golgi apparatus, S1P and S2P, even though their activation is triggered by different stimuli .…”

“…Interestingly, these ER membrane-bound transcription factors are cleaved by the same two proteases localized in the Golgi apparatus, S1P and S2P, even though their activation is triggered by different stimuli . SREBPs are translocated from the ER to the Golgi apparatus to be cleaved when cellular cholesterol levels decrease (DeBoseBoyd et al, 1999), whereas ATF6, OASIS and CREB-H relocate from the ER to the Golgi apparatus when unfolded proteins accumulate in the ER (Kondo et al, 2005;Okada et al, 2003;Shen et al, 2002;Zhang et al, 2006). By these means, diverse cellular function can be regulated by a single Rip mechanism.…”

FUS-CREB3L2/L1–Positive Sarcomas Show a Specific Gene Expression Profile with Upregulation of CD24 and FOXL1

“…9). On ER stress, the cleaved fragment which contains the bZIP domain is translocated to the nucleus where it may activate transcription more potently than the full-length protein through binding box-B sequences, ER stress-responsive elements, or cyclic AMP responsive elements (CRE) in the enhancers or promoters of target genes (10)(11)(12)(13). Previous data suggest that the FUS-CREB3L2 chimera is localized to the ER, cleaved by intramembrane proteolysis, and capable of activating transcription through box-B and CRE sequences and that it is a stronger transcriptional activator than wild-type (wt) CREB3L2 (13).…”

Endoplasmic reticulium protein profiling of heat-stressed Jurkat cells by one dimensional electrophoresis and liquid chromatography tandem mass spectrometry

“…Under ER stress, ER stress sensor PERK leads to activation of eIF2a, a key step in attenuation of protein translation (Kondo et al 2005). However, ER stress-induced phosphorylation of eIF2a can lead to selective translation of specific mRNAs encoding functions in modulating amino acid metabolism, anti-oxidative stress response, and apoptosis (Wek et al 2006).…”