Dissecting Pin1 and phospho-pRb regulation

Journal of Cellular Physiology
F RizzolioA Giordano

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.

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Citations

Aug 16, 2014·Cell Research·Zhimin Lu, Tony Hunter
Jan 30, 2013·Journal of Cellular Physiology·Riccardo Di FioreRenza Vento
Jan 31, 2019·Journal of Cellular Physiology·Concetta Russo SpenaFlavio Rizzolio
Dec 12, 2018·Frontiers in Pharmacology·Chi-Wai Cheng, Eric Tse
Jul 30, 2019·Frontiers in Pharmacology·Tiziano Tuccinardi, Flavio Rizzolio
Feb 7, 2019·Frontiers in Pharmacology·Maguie El BoustaniFlavio Rizzolio

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