Effects of tumor-associated mutations in the p53 tetramerization domain on oligomerization state and transcriptional activity
Effects of tumor-associated mutations in the p53 tetramerization domain on oligomerization state and transcriptional activity
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p53 四聚化结构域肿瘤相关突变对寡聚化状态和转录活性的影响
DOI：
10.1007/978-0-387-73657-0_249
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发表时间：
2009
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：
R. Kamada;T. Terai;T. Nomura;Y. Chuman;T. Imagawa;and K. Sakaguchi
肿瘤抑制蛋白p53通过反式激活参与不同细胞功能（如细胞周期阻滞和凋亡）的靶基因，在维持细胞应激的基因组完整性方面发挥重要作用[1]。p53通过C端四聚化结构域（TD）形成四聚体是其活性所必需的。p53四聚化结构域由β链（Glu326333）组成，这是一个紧转角，人类肿瘤在p53基因中携带失活突变。迄今为止，在四聚化结构域的31个残基中的22个位置中发现了41个点突变（图1B）。重要的是要了解通过四聚化结构域中的突变恶性转化的机制[2，3]。在这项研究中，我们进行了热力学分析的p53四聚体结构域肽与突变中发现的人类肿瘤，以澄清寡聚体结构的稳定性和转录活性的p53之间的定量相关性。
Tumor suppressor protein p53 plays an important role to maintain genomic integrity from cellular stress by transactivating the target genes involved in different cellular functions, such as cell cycle arrest and apoptosis [1]. The tetramer formation of p53 through the Cterminal tetramerization domain (TD) is essential for its activity. The p53 tetramerization domain consists of a βstrand (Glu326333), a tight turn human tumors carry inactivating mutations in the p53 gene. To date, 41 point mutations have been found in 22 positions among 31 residues of the tetramerization domain (Fig. 1B). It is important to understand the mechanism of malignant transformation by mutations in the tetramerization domain [2, 3]. In this study, we performed thermodynamic analysis of p53 tetramerization domain peptides with mutations found in human tumors in order to clarify the quantitative correlation between stability of oligomeric structure and transcriptional activity for p53.