Inhibition of tumor suppressor protein p53-dependent transcription by a tetramerization domain peptide via hetero-oligomerization
Inhibition of tumor suppressor protein p53-dependent transcription by a tetramerization domain peptide via hetero-oligomerization
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四聚化结构域肽通过异源寡聚化抑制肿瘤抑制蛋白 p53 依赖性转录
DOI：
10.1016/j.bmcl.2012.02.085
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
and K. Sakaguchi
中科院分区：
文献类型：
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作者：
J. Wada;R. Kamada;Y. Chuman;T. Imagawa;and K. Sakaguchi
肿瘤抑制蛋白p53诱导细胞周期停滞、凋亡和衰老以响应细胞应激。p53四聚体的形成对其功能至关重要。尽管p53对于基因组的完整性具有这些关键功能，但p53信号通路的激活导致低诱导多能干细胞（iPS）生成效率。在这项研究中，我们报告使用p53四聚化结构域肽，包含细胞穿透和核定位信号的p53依赖性转录的瞬时抑制。该肽被有效地引入细胞中，并通过与内源性p53蛋白的异源四聚体化抑制p21表达。该方法可应用于安全和有效的iPS细胞生成。
Tumor suppressor protein p53 induces cell cycle arrest, apoptosis, and senescence in response to cellular stresses. The p53 tetramer formation is essential for its functions. Despite of these crucial functions of p53 for integrity of genome, activation of the p53 signal pathway causes low induced pluripotent stem (iPS) cell generation efficiency. In this study, we report transient inhibition of p53-dependent transcription using a p53 tetramerization domain peptide that contains cell penetrating and nuclear localization signals. The peptide was efficiently introduced into cells and inhibited p21 expression via hetero-tetramerization with endogenous p53 protein. This method can be applied towards safe and efficient iPS cell generation.