The p53 protein is a novel substrate of ribosomal S6 kinase 2 and a critical intermediary for ribosomal S6 kinase 2 and histone H3 interaction
The p53 protein is a novel substrate of ribosomal S6 kinase 2 and a critical intermediary for ribosomal S6 kinase 2 and histone H3 interaction
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DOI：
10.1158/0008-5472.can-04-3935
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发表时间：
2005-05-01
期刊：
影响因子：
11.2
通讯作者：
Dong, ZG
中科院分区：
文献类型：
--
作者：
Cho, YY;He, ZW;Dong, ZG
肿瘤抑制蛋白p53是细胞信号转导通路中连接程度最高的节点之一，在控制细胞增殖和凋亡的网络中起着中心调节开关的作用。它参与基因的激活，维持对DNA错误（如DNA修复、染色体重组和染色体分离）的细胞反应的控制。在这里，我们发现核糖体S6激酶2 （RSK2）在体外和体内激活和磷酸化p53 (Ser(15))，并在细胞核中与p53共定位。p53缺失会减少rsk2介导的组蛋白H3（丝氨酸）磷酸化（10），而将p53添加回p53（-/-）胚胎成纤维细胞中可以恢复组蛋白H3丝氨酸磷酸化（10）。这些结果表明p53蛋白是RSK2的重要底物，也是RSK2和组蛋白H3相互作用的关键中介。rsk2 -p53-组蛋白H3复合物可能参与染色质重塑和细胞周期调节。
The tumor suppressor p53 protein is one of the most highly connected nodes in cellular signal transduction pathways and acts as a central regulatory switch in networks controlling cell proliferation and apoptosis. It is involved in the activation of genes that maintain control over cellular responses to DNA errors such as DNA repair, chromosomal recombination, and chromosome segregation. Here we show that ribosomal S6 kinase 2 (RSK2) activates and phosphorylates p53 (Ser(15)) in vitro and in vivo and colocalizes with p53 in the nucleus. Deficiency of p53 diminishes RSK2-mediated phosphorylation of histone H3 (Ser(10)) and adding back p53 to p53(-/-) embryonic fibroblasts restored phosphorylation of histone H3 at Ser(10). These results show that the p53 protein is an important substrate of RSK2 and a critical intermediary in the RSK2 and histone H3 interaction. The RSK2-p53-histone H3 complex may likely contribute to chromatin remodeling and cell cycle regulation.