SEQUENCE-SPECIFIC TRANSCRIPTIONAL ACTIVATION IS ESSENTIAL FOR GROWTH SUPPRESSION BY P53
SEQUENCE-SPECIFIC TRANSCRIPTIONAL ACTIVATION IS ESSENTIAL FOR GROWTH SUPPRESSION BY P53
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DOI：
10.1073/pnas.91.6.1998
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发表时间：
1994-03-15
影响因子：
11.1
通讯作者：
VOGELSTEIN, B
中科院分区：
文献类型：
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作者：
PIETENPOL, JA;TOKINO, T;VOGELSTEIN, B
虽然p53的几个生化特征已被描述，但它们与肿瘤抑制的关系仍不确定。我们比较了p53衍生蛋白作为序列特异性转录（SST）激活剂的能力，其抑制肿瘤细胞生长的能力，使用改进的生长抑制试验。天然存在的和体外衍生的突变都消除了p53的SST活性，失去了抑制肿瘤细胞生长的能力。此外，p53的N末端和C末端在功能上分别被外源反式激活和二聚化结构域取代，同时一致地保留了SST和肿瘤抑制特性。只有p53的中心区域，赋予特异性DNA结合，需要抑制生长的杂交蛋白。因此，p53的SST活性似乎是该蛋白作为肿瘤抑制因子发挥功能所必需的。
Although several biochemical features of p53 have been described, their relationship to tumor suppression remains uncertain. We have compared the ability of p53-derived proteins to act as sequence-specific transcriptional (SST) activators with their ability to suppress tumor cell growth, using an improved growth-suppression assay. Both naturally occurring and in vitro derived mutations that abrogated the SST activity of p53 lost the ability to suppress tumor cell growth. Additionally, the N- and C-terminal ends of p53 were shown to be functionally replaceable with foreign transactivation and dimerization domains, respectively, with concordant preservation of both SST and tumor-suppressive properties. Only the central region of p53, conferring specific DNA binding, was required to suppress growth by such hybrid proteins. The SST activity of p53 thus appeared to be essential for the protein to function as a tumor suppressor.