ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of golgi localization signals
ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of golgi localization signals
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DOI：
10.1016/s1534-5807(02)00203-4
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发表时间：
2002-07-01
影响因子：
11.8
通讯作者：
Prywes, R
中科院分区：
文献类型：
--
作者：
Shen, JS;Chen, X;Prywes, R
ATF 6是一种内质网（ER）应激调节的跨膜转录因子，可激活ER分子伴侣的转录。在ER应激时，ATF 6从ER易位到高尔基体，在那里它被加工成其活性形式。我们已经发现ER伴侣BiP/GRP 78结合ATF 6并响应于ER应激而解离。BiP结合的丧失与ATF 6向高尔基体的易位相关，这在过表达BiP的细胞中减慢。两个高尔基定位信号（GLS）中确定的ATF 6。从ATF 6中去除BiP结合位点，同时保留GLS，导致其组成性易位到高尔基体。这些结果表明，BiP通过抑制其GLS将ATF 6保留在ER中，并且在ER应激期间BiP的解离允许ATF 6被转运到高尔基体。
ATF6 is an endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor that activates the transcription of ER molecular chaperones. Upon ER stress, ATF6 translocates from the ER to the Golgi where it is processed to its active form. We have found that the ER chaperone BiP/GRP78 binds ATF6 and dissociates in response to ER stress. Loss of BiP binding correlates with the translocation of ATF6 to the Golgi, which was slowed in cells overexpressing BiP. Two Golgi localization signals (GLSs) were identified in ATF6. Removal of BiP binding sites from ATF6, while retaining a GLS, resulted in its constitutive translocation to the Golgi. These results suggest that BiP retains ATF6 in the ER by inhibiting its GLSs and that dissociation of BiP during ER stress allows ATF6 to be transported to the Golgi.