title: Dissecting Pin1 and phospho-pRb regulation.
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.
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA.
authors.forename: Flavio
authors.initials: F
authors.lastname: Rizzolio
authors.forename: Isabella
authors.initials: I
authors.lastname: Caligiuri
authors.forename: Chiara
authors.initials: C
authors.lastname: Lucchetti
authors.forename: Robert
authors.initials: R
authors.lastname: Fratamico
authors.forename: Valentina
authors.initials: V
authors.lastname: Tomei
authors.forename: Gaia
authors.initials: G
authors.lastname: Gallo
authors.forename: Alexis
authors.initials: A
authors.lastname: Agelan
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ferrari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
authors.forename: Andres J
authors.initials: AJ
authors.lastname: Klein-Szanto
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016543:Central Nervous System Neoplasms / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D005910:Glioma / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016160:Retinoblastoma Protein; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse