OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes
OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes
复制标题
DOI：
10.1038/ncb1213
复制
发表时间：
2005-02-01
影响因子：
21.3
通讯作者：
Imaizumi, K
中科院分区：
文献类型：
--
作者：
Kondo, S;Murakami, T;Imaizumi, K
众所周知，当未折叠蛋白在内质网中积累时，内质网 (ER) 应激传感器 IRE1、PERK 和 ATF6 将信号从 ER 转导至细胞质和细胞核。在这里，我们将 OASIS 确定为一种新型 ER 应激传感器。 OASIS 是 CREB/ATF 家族的一种基本亮氨酸拉链 (bZIP) 转录因子，具有跨膜结构域，可使其与 ER 结合。该分子响应 ER 应激而在膜上裂解，其裂解的氨基末端胞质结构域（包含 bZIP 结构域）易位到细胞核中，在细胞核中激活由 ER 应激反应元件和环 AMP 反应元件介导的靶基因的转录。有趣的是，OASIS 在中枢神经系统星形胶质细胞 ER 应激期间在转录水平上被诱导，但在所检查的其他细胞类型中则不然。此外，OASIS 的过度表达导致 BiP 的诱导和 ER 应激诱导的细胞死亡的抑制，而敲低则部分降低 BiP 水平并导致易感星形胶质细胞的 ER 应激。我们的结果揭示了 OASIS 在调节星形胶质细胞中未折叠蛋白反应中的关键作用，以及细胞类型特异性 UPR 信号传导也存在于其他细胞中的可能性。
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.