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来自哥伦比亚大学医学中心癌症遗传学研究所和病理细胞生物学系的顾伟教授以及Jan-Philipp Kruse共同在最新一期的Cell上发表P53研究综述文章:Modes of p53 Regulation。 传统的观点认为p53激活路径分三步，1. p53蛋白稳定化（p53 stabilization）；2. 与DNA结合（DNA binding）；3. 转录激活（Transcriptional activation）。然而，旧的理论已经不再适应新的研究结论，研究发现p53激活路径中每一步都比我们所想象的要复杂得多。 以小鼠为模型的活体遗传性研究和体外实验研究结果表明，传统的观点不能解释很多现象，因此为了全面建立p53的调节网路理论，我们必须更新对p53的看法。 顾伟提出，抗阻抑作用（释放细胞因子，如Mdm2和MdmX，防止p53释放受阻）是激活p53的关键步骤。 推荐原始出处： Cell, 15 May 2009 doi:10.1016/j.cell.2009.04.050 Modes of p53 Regulation Jan-Philipp Kruse1,2andWei Gu1,2,, 1 Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, 1130 St. Nicholas Avenue, New York, NY 10032, USA 2 Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 1130 St. Nicholas Avenue, New York, NY 10032, USA Summary The traditional view of p53 activation includes three stepsp53 stabilization, DNA binding, and transcriptional activation. However, recent studies indicate that each step of p53 activation is more complex than originally anticipated. Moreover, both genetic studies in mice and in vitro studies with purified components suggest that the classical model may not be sufficient to explain all aspects of p53 activation in vivo. To reconcile these differences, we propose that antirepression, the release of p53 from repression by factors such as Mdm2 and MdmX, is a key step in the physiological activation of p53. (责任编辑：Doctor001) |
