THE DNA-BINDING DOMAIN OF P53 CONTAINS THE 4 CONSERVED REGIONS AND THE MAJOR MUTATION HOT-SPOTS
THE DNA-BINDING DOMAIN OF P53 CONTAINS THE 4 CONSERVED REGIONS AND THE MAJOR MUTATION HOT-SPOTS
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DOI：
10.1101/gad.7.12b.2556
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发表时间：
1993-12-01
影响因子：
10.5
通讯作者：
PABO, CO
中科院分区：
文献类型：
--
作者：
PAVLETICH, NP;CHAMBERS, KA;PABO, CO
p53 肿瘤抑制基因突变是人类癌症中最常见的基因改变。大多数突变发生在基因的保守中心部分，但有关该区域功能的信息很少。通过对 393 个氨基酸的人 p53 蛋白进行蛋白水解消化，我们鉴定出了对应于 p53 中心部分的 191 个氨基酸的蛋白酶抗性片段（残基 102-292），并且我们表明该核心片段是该蛋白的序列特异性 DNA 结合结构域。 DNA 结合受到金属螯合剂的抑制，我们发现核心结构域含有锌。蛋白水解消化还揭示了 53 个氨基酸的羧基末端结构域，我们证明它是 p53 的四聚化结构域。
Mutations in the p53 tumor suppressor gene are the most commonly observed genetic alterations in human cancer. The majority of these mutations occur in the conserved central portion of the gene, but there has been little information about the function of this region. Using proteolytic digestion of the 393-amino-acid human p53 protein, we have identified a 191-amino-acid protease-resistant fragment (residues 102-292) that corresponds to the central portion of p53, and we show that this core fragment is the sequence-specific DNA-binding domain of the protein. DNA binding is inhibited by metal chelating agents, and we find that the core domain contains zinc. Proteolytic digests also reveal a 53-amino-acid carboxy-terminal domain which we show to be the tetramerization domain of p53.