Deregulated expression of pro-survival and pro-apoptotic p53-dependent genes upon Elongator deficiency in colon cancer cells
Deregulated expression of pro-survival and pro-apoptotic p53-dependent genes upon Elongator deficiency in colon cancer cells
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DOI：
10.1016/j.bcp.2008.03.006
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发表时间：
2008-06-01
影响因子：
5.8
通讯作者：
Chariot, Alain
中科院分区：
文献类型：
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作者：
Cornez, Isabelle;Creppe, Catherine;Chariot, Alain
伸长子是由IkappaB激酶相关蛋白(IKAP)/hELP1支架蛋白组装的多亚基复合物，参与细胞核的转录伸长以及细胞质中的tRNA修饰。然而，细长体在人类细胞中调控的生物学过程才刚刚开始被阐明。在这里，我们证明IKAP/hELP1缺失的结肠癌来源细胞显示一些促凋亡p53依赖基因（如BAX）的基础表达增强，但不是全部。此外，拉长体缺乏通过p53依赖途径导致基础和道诺霉素诱导的促生存血清和糖皮质激素诱导的蛋白激酶（SGK）基因的表达增加。因此，我们的数据共同表明，伸长体缺乏触发p53依赖基因的激活，这些基因在细胞凋亡方面具有相反的功能。(C) 2008爱思唯尔公司版权所有。
Elongator, a multi-subunit complex assembled by the IkappaB kinase-associated protein (IKAP)/hELP1 scaffold protein is involved in transcriptional elongation in the nucleus as well as in tRNA modifications in the cytoplasm. However, the biological processes regulated by Elongator in human cells only start to be elucidated. Here we demonstrate that IKAP/hELP1 depleted colon cancer-derived cells show enhanced basal expression of some but not all pro-apoptotic p53-dependent genes such as BAX. Moreover, Elongator deficiency causes increased basal and daunomycin-induced expression of the pro-survival serum- and glucocorticoid-induced protein kinase (SGK) gene through a p53-dependent pathway. Thus, our data collectively demonstrate that Elongator deficiency triggers the activation of p53-dependent genes harbouring opposite functions with respect to apoptosis. (C) 2008 Elsevier Inc. All rights reserved.