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Rizzolio F , Caligiuri I , Lucchetti C , Fratamico R , Tomei V , Gallo G , Agelan A , Ferrari G , Toffoli G , Klein-Szanto AJ , Giordano A
Dissecting Pin1 and phospho-pRb regulation
Journal of Cellular Physiology. 2013 Jan;228(1) :73-77
PMID: WOS:000309678000011   
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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: 7377, 2013. (c) 2012 Wiley Periodicals, Inc.
Notes
Rizzolio, Flavio Caligiuri, Isabella Lucchetti, Chiara Fratamico, Robert Tomei, Valentina Gallo, Gaia Agelan, Alexis Ferrari, Giovanni Toffoli, Giuseppe Klein-Szanto, Andres J. Giordano, Antonio Associazione Italiana per la Ricerca sul Cancro (AIRC); Special Program Molecular Clinical Oncology [12214]; European Research Council [269051]; Sbarro Health Research Organization; Human Health Foundation; Istituto Toscano Tumori; Commonwealth of Pennsylvania Contract grant sponsor: Associazione Italiana per la Ricerca sul Cancro (AIRC).Contract grant sponsor: Special Program Molecular Clinical Oncology;Contract grant number: 12214.Contract grant sponsor: European Research Council;Contract grant number: 269051.Contract grant sponsor: Sbarro Health Research Organization.Contract grant sponsor: Human Health Foundation.Contract grant sponsor: Istituto Toscano Tumori.Contract grant sponsor: Commonwealth of Pennsylvania. 45 Wiley-blackwell Hoboken 018qw