Shen Jingshi, Chen Xi, Hendershot Linda, Prywes Ron
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Dev Cell. 2002 Jul;3(1):99-111. doi: 10.1016/s1534-5807(02)00203-4.
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.
ATF6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。在内质网应激时，ATF6从内质网转运至高尔基体，在那里被加工成其活性形式。我们发现内质网伴侣BiP/GRP78结合ATF6并在内质网应激时解离。BiP结合的丧失与ATF6向高尔基体的转运相关，在过表达BiP的细胞中这种转运减慢。在ATF6中鉴定出两个高尔基体定位信号（GLS）。从ATF6中去除BiP结合位点，同时保留一个GLS，导致其组成型转运至高尔基体。这些结果表明BiP通过抑制其GLS将ATF6保留在内质网中，并且在内质网应激期间BiP的解离允许ATF6转运至高尔基体。
