Novel Cis-acting Element GASE Regulates Transcriptional Induction by the Golgi Stress Response
Novel Cis-acting Element GASE Regulates Transcriptional Induction by the Golgi Stress Response
复制标题
DOI：
10.1247/csf.10014
复制
发表时间：
2011-01-01
影响因子：
1.5
通讯作者：
Yoshida, Hiderou
中科院分区：
文献类型：
--
作者：
Oku, Masaya;Tanakura, Soichiro;Yoshida, Hiderou
当分泌蛋白的产生增加破坏了内质网（ER）和高尔基体的能力时，真核细胞扩大了它们维持分泌功能的能力。ER的能力通过称为ER应激反应的机制增强，但是调节高尔基体能力（高尔基体应激反应）的机制仍然不清楚。在这里，我们发现，高尔基体相关基因的转录，包括糖基化酶以及参与后高尔基体囊泡运输和高尔基体结构的维护的因素，上调后处理莫能菌素，离子载体，破坏酸性细胞器，包括高尔基体和溶酶体的功能，通过中和它们的内腔。这种转录诱导被发现通常是由一个新的顺式作用元件称为高尔基体应激反应元件（GASE），其共识序列是ACGTGgc。当高尔基体的功能被GCP60（一种与Giantin结合的高尔基体定位蛋白）的过表达特异性干扰时，GASE的转录被显著诱导。这些结果表明，哺乳动物细胞有高尔基应激反应，GASE调节转录诱导参与高尔基应激反应。
When increased production of secretory proteins overwhelms the capacity of the endoplasmic reticulum (ER) and the Golgi apparatus, eukaryotic cells expand their capacity to sustain secretory function. The capacity of the ER is enhanced by the mechanism called the ER stress response, but the mechanism regulating Golgi capacity (the Golgi stress response) has remained unclear. Here, we found that transcription of Golgi-related genes, including glycosylation enzymes as well as factors involved in post-Golgi vesicular transport and maintenance of Golgi structure, was upregulated upon treatment with monensin, an ionophore that disrupts the function of acidic organelles, including the Golgi apparatus and lysosomes by neutralizing their lumen. This transcriptional induction was found to be commonly regulated by a novel cis-acting element called the Golgi apparatus stress response element (GASE), whose consensus sequence is ACGTGgc. When the function of the Golgi apparatus was specifically disturbed by overexpression of GCP60, a Golgi-localized protein that binds to giantin, transcription from GASE was significantly induced. These results suggest that mammalian cells have the Golgi stress response, and that GASE regulates transcriptional induction involved in the Golgi stress response.