Role of Herp in the endoplasmic reticulum stress response
Role of Herp in the endoplasmic reticulum stress response
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DOI：
10.1111/j.1356-9597.2004.00735.x
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发表时间：
2004-05-01
期刊：
影响因子：
2.1
通讯作者：
Ogawa, S
中科院分区：
文献类型：
--
作者：
Hori, O;Ichinoda, F;Ogawa, S
应用差异显示技术对培养的大鼠星形胶质细胞进行Herp cDNA克隆。虽然Herp强烈诱导内质网（ER）的压力，它迅速衰减随之而来的蛋白酶体介导的降解。为了研究该分子在应激反应中的作用，使用F9胚胎癌细胞开发了Herp敲除细胞。与F9野生型细胞相比，F9 Herp缺失细胞更容易受到ER应激的影响。在ER应激的早期（衣霉素处理后0-8 h），与野生型细胞相比，Herp null细胞显示增强的ER应激信号传导和内源性ERAD底物的稳定。在中期（衣霉素处理后8-20小时），Herp无效细胞显示减少的ER应激信号传导，而在晚期（衣霉素处理后20-40小时），Herp无效细胞表现出导致凋亡性细胞死亡的不可逆细胞变化。转染分析表明，N-末端区域，包括泛素样结构域的Herp，是所需的F9细胞在ER应激下的生存。这些结果表明，Herp是一种短寿命的Ub样蛋白，改善了ER中折叠能力和蛋白负载的平衡，并在F9细胞中的ER应激抗性中起着至关重要的作用。
Application of differential display to cultured rat astrocytes allowed cloning of Herp cDNA. Although Herp was strongly induced by endoplasmic reticulum (ER) stress, it decayed rapidly consequent to proteasome-mediated degradation. To investigate the role of this molecule in terms of the stress response, Herp knockout cells were developed using F9 embryonic carcinoma cells. F9 Herp null cells were more vulnerable to ER stress compared with F9 wild-type cells. In the early period of ER stress (0-8 h after tunicamycin treatment), Herp null cells displayed enhanced ER stress signalling and stabilization of an endogenous ERAD substrate, compared with wild-type cells. In the intermediate period (8-20 h after tunicamycin treatment), Herp null cells displayed reduced ER stress signalling, whereas in the late period (20-40 h after tunicamycin treatment), Herp null cells manifested irreversible cellular changes that lead to apoptotic cell death. Transfection analysis revealed that the N-terminal region, including the ubiquitin-like domain of Herp, was required for the survival of F9 cells under ER stress. These results indicate that Herp is a short-lived Ub-like protein improving the balance of folding capacity and protein loads in the ER and plays crucial roles for the ER stress resistance in F9 cells.