adapt78 protects cells against stress damage and suppresses cell growth
adapt78 protects cells against stress damage and suppresses cell growth
复制标题
DOI：
10.1006/abbi.2000.1897
复制
发表时间：
2000-07-15
影响因子：
3.9
通讯作者：
Crawford, DR
中科院分区：
文献类型：
--
作者：
Leahy, KP;Crawford, DR
我们以前已经鉴定了几个基因，它们的RNA产物在观察到细胞保护性适应性反应的条件下在HA-1仓鼠细胞中被诱导。其中一个基因，命名为Adapt78，被发现与人类的葡萄糖调节蛋白78(GRP78)有一些同源。我们随后确定Adapt78和GRP78mRNAs是由相同的应激剂诱导的，并得出结论，Adapt78是一个应激反应基因，可能是GRP应激基因家族中的新成员。在这里，我们扩展这些研究，以评估过度表达Adapt78对压力保护和生长停滞的影响。与对照组相比，稳定表达Adapt78基因的HA-1细胞对钙离子和过氧化氢介导的细胞毒作用显著降低。此外，Adapt78稳定过表达的细胞显示出显著的抑制细胞生长。细胞保护和生长停滞都只伴随着Adapt78的适度过度表达。流式细胞仪检测显示细胞生长停滞于G(1)期。免疫荧光分析显示，Adapt78蛋白除了胞浆定位外，还表现出明显的核周染色，提示内质网定位。这些数据表明，Adapt78既有细胞保护作用，又有生长抑制作用，这些作用可能是由内质网的Adapt78蛋白介导的。(C)2000年学术出版社。
We have previously identified several genes whose RNA products are induced in HA-1 hamster cells under conditions where a cytoprotective adaptive response is observed. One of these genes, designated adapt78, was found to have a human homolog with some homology to glucose-regulated protein 78 (Grp78). We subsequently determined that adapt78 and grp78 mRNAs are induced by the same stress agents and conclude that adapt78 is a stress-response gene and putative new member of the grp stress gene family. Here we extend these studies to assess the effect of overexpressing adapt78 on stress protection and growth arrest. HA-1 cells stably transfected with adapt78 cDNA were found to exhibit significantly reduced calcium- and hydrogen peroxide-mediated cytotoxicity as compared with control transfectants. In addition, adapt78 stable overexpressors exhibited significantly reduced cell growth. Both cytoprotection and growth arrest accompanied only modest overexpression of adapt78. Flow cytometry revealed that the growth arrest occurred in G(1)-phase. Immunoflourescent analysis revealed that Adapt78 protein exhibits significant perinuclear staining suggestive of endoplasmic reticulum localization in addition to cytoplasmic localization. These data indicate that adapt78 is both cytoprotective and growth suppressive and that these effects may be mediated by Adapt78 protein at the endoplasmic reticulum. (C) 2000 Academic Press.