Cleavage of the membrane-bound transcription factor OASIS in response to endoplasmic reticulum stress
Cleavage of the membrane-bound transcription factor OASIS in response to endoplasmic reticulum stress
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DOI：
10.1111/j.1471-4159.2005.03596.x
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发表时间：
2006-02-01
影响因子：
4.7
通讯作者：
Imaizumi, K
中科院分区：
文献类型：
--
作者：
Murakami, T;Kondo, S;Imaizumi, K
当未折叠或错误折叠的蛋白质在内质网（ER）中积累时，未折叠蛋白质反应（UPR）信号从ER传递到细胞核和细胞质以促进蛋白质折叠。OASIS（old astrocyte specifically induced substance）是星形胶质细胞中的ER应激转导子，是一种膜结合转录因子，其激活ER应激反应中的基因。当未折叠的蛋白质在ER中积累时，OASIS在膜上被切割以释放其胞质结构域，然后进入细胞核并激活靶基因。在这里，我们表明，OASIS是由站点-1和-2蛋白酶（S1 P和S2 P），酶驻留在高尔基体和过程激活转录因子6（ATF 6）响应ER压力。我们还表明，OASIS的切割是通过其移位到高尔基体而触发的。所有的OASIS管腔结构域的缺失突变体显示，蛋白水解加工和移位到高尔基体保持完整，表明OASIS不具有显著的序列的高尔基体定位信号，不同的情况下的ATF 6，并可能有其他系统的OASIS移位到高尔基体响应ER压力。
When unfolded or misfolded proteins accumulate in the endoplasmic reticulum (ER), unfolded protein response (UPR) signals are transmitted from the ER to the nucleus and cytoplasm to facilitate protein folding. OASIS (old astrocyte specifically induced substance) is an ER stress transducer in astrocytes, a membrane-bound transcription factor that activates genes in the ER stress response. When unfolded proteins accumulate in the ER, OASIS is cleaved at the membrane to release its cytoplasmic domain, which then enters the nucleus and activates target genes. Here, we showed that OASIS is processed by Site-1 and -2 proteases (S1P and S2P), enzymes that reside at the Golgi apparatus and process activating transcription factor 6 (ATF6) in response to ER stress. We also showed that the cleavage of OASIS is triggered by its translocation to the Golgi apparatus. All deletion mutants for luminal domain of OASIS showed that proteolytic processing and translocation to the Golgi apparatus remained intact, indicating that OASIS does not have significant sequences for Golgi localization signals, different from the case of ATF6, and that there could be other systems for translocation of OASIS to the Golgi apparatus in response to ER stress.