Dissecting Pin1 and phospho‐pRb regulation |
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| Authors: | Flavio Rizzolio Isabella Caligiuri Chiara Lucchetti Robert Fratamico Valentina Tomei Gaia Gallo Alexis Agelan Giovanni Ferrari Giuseppe Toffoli Andres J Klein‐Szanto Antonio Giordano |
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| Institution: | 1. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania;2. Experimental and Clinical Pharmacology, National Cancer Institute IRCCS Aviano, Aviano, Italy;3. Department of Human Pathology and Oncology, University of Siena, Siena, Italy;4. Human Health Foundation, Terni and Spoleto (PG), Spoleto, Italy;5. Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania;6. Department of Pathology, Fox‐Chase Cancer Center, Philadelphia, Pennsylvania |
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| Abstract: | 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. J. Cell. Physiol. 228: 73–77, 2013. © 2012 Wiley Periodicals, Inc. |
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