RCAN1.4 的敲低通过上调 p53 表达增加了对 FAS 介导的和 DNA 损伤诱导的细胞凋亡的敏感性。
Knockdown of RCAN1.4 Increases Susceptibility to FAS-mediated and DNA-damage-induced Apoptosis by Upregulation of p53 Expression.
机构信息
Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
出版信息
Korean J Physiol Pharmacol. 2009 Dec;13(6):483-9. doi: 10.4196/kjpp.2009.13.6.483. Epub 2009 Dec 31.
Abstract
Despite the potential importance of the human regulator of calcineurin 1 (RCAN-1) gene in the modulation of cell survival under stress, little is known about its role in death-inducing signal pathways. In this study, we addressed the effects of RCAN1.4 knockdown on cellular susceptibility to apoptosis and the activation of death pathway proteins. Transfection of siRNAs against RCAN1.4 resulted in enhanced Fas- and etoposide-induced apoptosis, which was associated with increased expression and translocation of Bax to mitochondria. Our results suggest that enhanced expression and activation of p53 was responsible for the upregulation of Bax and the increased sensitivity to apoptosis, which could be reversed by p53 knockdown. To explain the observed upregulation of p53, we propose a downregulation of the ubiquitin ligase HDM2, probably translationally. These findings show the importance of appropriate RCAN1.4 expression in the modulation of cell survival and reveal a link between RCAN1.4 and p53.
摘要
尽管钙调神经磷酸酶 1（RCAN-1）基因在应激条件下调节细胞存活方面具有重要意义，但人们对其在诱导细胞死亡信号通路中的作用知之甚少。在本研究中，我们探讨了 RCAN1.4 敲低对细胞凋亡易感性和死亡途径蛋白激活的影响。针对 RCAN1.4 的 siRNA 转染导致 Fas 和依托泊苷诱导的细胞凋亡增加，这与 Bax 向线粒体的表达和易位增加有关。我们的结果表明，p53 的表达和激活增强导致 Bax 的上调和对细胞凋亡的敏感性增加，p53 敲低可逆转这种现象。为了解释观察到的 p53 上调，我们提出了泛素连接酶 HDM2 的下调，可能是翻译后水平的下调。这些发现表明适当的 RCAN1.4 表达在调节细胞存活方面的重要性，并揭示了 RCAN1.4 与 p53 之间的联系。
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