Proteins of the S100 family regulate the oligomerization of p53 tumor suppressor
Proteins of the S100 family regulate the oligomerization of p53 tumor suppressor
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DOI：
10.1073/pnas.0501459102
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发表时间：
2005-03-29
影响因子：
11.1
通讯作者：
Fersht, AR
中科院分区：
文献类型：
--
作者：
Fernandez-Fernandez, MR;Veprintsev, DB;Fersht, AR
S100B蛋白在早期阿尔茨海默病和唐氏综合症患者的大脑中升高。S100A4与转移的发生有关。这两种蛋白都与p53肿瘤抑制因子结合。我们发现S100B和S100A4仅在低寡聚化状态下与p53的四聚化结构域（残基325-355）结合，因此它们破坏p53的四聚化。此外，S100B与负调控域和核定位域结合，导致与p53蛋白序列紧密结合，暴露其C端的四聚域。由于p53的转运取决于其寡聚化状态，我们认为S100B和S100A4可以调节p53的亚细胞定位。但是，这些蛋白与p53结合方式的差异可能导致S100B和S1004对p53在细胞周期控制中的功能有不同的影响。
S100B protein is elevated in the brains of patients with early stages of Alzheimer's disease and Down's syndrome. S100A4 is correlated with the development of metastasis. Both proteins bind to p53 tumor suppressor. We found that both S100B and S100A4 bind to the tetramerization domain of p53 (residues 325-355) only when exposed in lower oligomerization states and so they disrupt the tetramerization of p53. In addition, S100B binds to the negative regulatory and nuclear localization domains, which results in a very tight binding to p53 protein sequences that exposed the tetramerization domain in their C terminus. Because the trafficking of p53 depends on its oligomerization state, we suggest that S100B and S100A4 could regulate the subcellular localization of p53. But, the differences in the way these proteins bind to p53 could result in S100B and S1004 having different effects on p53 function in cell-cycle control.