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來自哥倫比亞大學(xué)醫(yī)學(xué)中心癌癥遺傳學(xué)研究所和病理細(xì)胞生物學(xué)系的顧偉教授以及Jan-Philipp Kruse共同在最新一期的Cell上發(fā)表P53研究綜述文章:Modes of p53 Regulation。 傳統(tǒng)的觀點(diǎn)認(rèn)為p53激活路徑分三步，1. p53蛋白穩(wěn)定化（p53 stabilization）；2. 與DNA結(jié)合（DNA binding）；3. 轉(zhuǎn)錄激活（Transcriptional activation）。然而，舊的理論已經(jīng)不再適應(yīng)新的研究結(jié)論，研究發(fā)現(xiàn)p53激活路徑中每一步都比我們所想象的要復(fù)雜得多。 以小鼠為模型的活體遺傳性研究和體外實(shí)驗(yàn)研究結(jié)果表明，傳統(tǒng)的觀點(diǎn)不能解釋很多現(xiàn)象，因此為了全面建立p53的調(diào)節(jié)網(wǎng)路理論，我們必須更新對(duì)p53的看法。 顧偉提出，抗阻抑作用（釋放細(xì)胞因子，如Mdm2和MdmX，防止p53釋放受阻）是激活p53的關(guān)鍵步驟。 推薦原始出處： 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. (責(zé)任編輯：Doctor001) |
