Interactions of the p53 protein family in cellular stress response in gastrointestinal tumors.
Interactions of the p53 protein family in cellular stress response in gastrointestinal tumors.
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DOI：
10.1158/1535-7163.mct-09-0912
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发表时间：
2010-03
影响因子：
5.7
通讯作者：
Zaika AI
中科院分区：
文献类型：
--
作者：
Vilgelm AE;Washington MK;Wei J;Chen H;Prassolov VS;Zaika AI
P53、P63和P73是P53蛋白家族的成员，参与调节细胞周期、细胞凋亡、细胞分化和其他关键的细胞过程。在这里，我们调查了整个P53家族在胃肠道肿瘤化疗药物反应中的作用。实时定量聚合酶链式反应和免疫组织化学显示P53蛋白家族表达谱的复杂性和变异性。使用结肠和食道癌细胞，我们发现，通过报告分析测量的整个p53家族的整合转录活性与研究细胞对药物治疗的反应有关。我们还发现P53和P73以及P63和P73同时与P53靶基因的启动子结合。综上所述，我们的结果支持这样的观点，即P53蛋白家族作为一个相互作用的蛋白质网络发挥作用，并表明细胞对化疗药物治疗的反应取决于整个P53家族的总活性，而不仅仅是P53本身。
p53, p63 and p73 are members of the p53 protein family involved in regulation of cell cycle, apoptosis, differentiation and other critical cellular processes. Here we investigated the contribution of the entire p53 family in chemotherapeutic drug response in gastrointestinal tumors. Real-time PCR and immunohistochemistry revealed complexity and variability of expression profiles of the p53 protein family. Using colon and esophageal cancer cells, we found that the integral transcription activity of the entire p53 family, as measured by the reporter analysis, associated with response to drug treatment in studied cells. We also found that p53 and p73, as well as p63 and p73, bind simultaneously to the promoters of p53 target genes. Taken together, our results support the view that the p53 protein family functions as an interacting network of proteins and show that cellular responses to chemotherapeutic drug treatment are determined by the total activity of the entire p53 family, rather than p53 alone.