Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA.
J Cell Physiol. 2013 Jan;228(1):73-7. doi: 10.1002/jcp.24107.
The activity of the Retinoblastoma protein, the master regulator of the cell cycle, is finely regulated by phosphorylation. CDKs and cyclins are major players in phosphorylation and it has been recently discovered that the prolyl isomerase Pin1 is an essential protein that orchestrates this process. In this article, we report new findings regarding the role of Pin1 in the pRb pathway. Our data suggest that PI3K, CDKs, and the Pin1 axis have a critical role in sustaining the complete phosphorylation of pRb. Furthermore, we analyze the correlation between Pin1 and pRb phosphorylation in vivo. We show that, in human malignant glioma tissue microarrays (TMA) and in Pin1 knockout (KO) mice, there is a positive correlation between Pin1 and pRb phosphorylation. Prospectively, our findings suggest that the synergism between CDKs, Pin1, and PI3K inhibitors hold great promise for targeted pharmacological treatment of cancer patients, with the possibility of reaching high effectiveness at tolerated doses.
视网膜母细胞瘤蛋白（Retinoblastoma protein）是细胞周期的主要调控因子，其活性受到磷酸化的精细调控。细胞周期蛋白依赖性激酶（CDKs）和细胞周期蛋白是磷酸化的主要参与者，最近发现脯氨酰顺反异构酶 Pin1 是协调这一过程的必需蛋白。在本文中，我们报告了关于 Pin1 在 pRb 通路中作用的新发现。我们的数据表明，PI3K、CDKs 和 Pin1 轴在维持 pRb 的完全磷酸化中起着关键作用。此外，我们分析了体内 Pin1 和 pRb 磷酸化之间的相关性。我们表明，在人类恶性神经胶质瘤组织微阵列（TMA）和 Pin1 敲除（KO）小鼠中，Pin1 和 pRb 磷酸化之间存在正相关。有前景的是，我们的发现表明，CDKs、Pin1 和 PI3K 抑制剂的协同作用为癌症患者的靶向药物治疗提供了巨大的希望，有可能在可耐受的剂量下达到高疗效。
