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Androgen receptor serine 81 mediates Pin1 interaction and activity
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Volume 11, Issue 18 September 15, 2012
Pages 3415 - 3420
http://dx.doi.org/10.4161/cc.21730
Keywords: ARSer81, Pin1, androgen receptor, phosphorylation, prostate cancer
Authors: Raffaele La Montagna, Isabella Caligiuri, Pasquale Maranta, Chiara Lucchetti, Luca Esposito, Marco G. Paggi, Giuseppe Toffoli, Flavio Rizzolio and Antonio Giordano
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- Raffaele La Montagna
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Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA; Human Health Foundation; Terni and Spoleto, Perugia, Italy
These authors have equally contributed to this work.
- Isabella Caligiuri
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Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA; Human Health Foundation; Terni and Spoleto, Perugia, Italy; Department of Human Pathology and Oncology; University of Siena; Siena, Italy
These authors have equally contributed to this work.
- Pasquale Maranta
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Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA
- Chiara Lucchetti
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Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA
- Luca Esposito
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INT-CROM; Pascale Foundation; National Cancer Institute - Cancer Research Center; Mercogliano, Italy
- Marco G. Paggi
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National Cancer Institute Regina Elena; Rome, Italy
- Giuseppe Toffoli
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Division of Experimental and Clinical Pharmacology; Department of Molecular Biology and Translational Research; National Cancer Institute and Center for Molecular Biomedicine; Aviano, Pordenone, Italy
- Flavio Rizzolio
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Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA; Division of Experimental and Clinical Pharmacology; Department of Molecular Biology and Translational Research; National Cancer Institute and Center for Molecular Biomedicine; Aviano, Pordenone, Italy
- Antonio Giordano
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Corresponding author: giordano@temple.edu
Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA; Human Health Foundation; Terni and Spoleto, Perugia, Italy; Department of Human Pathology and Oncology; University of Siena; Siena, Italy; INT-CROM; Pascale Foundation; National Cancer Institute - Cancer Research Center; Mercogliano, Italy
Abstract:
Hormone-dependent tumors are characterized by deregulated activity of specific steroid receptors, allowing aberrant expression of many genes involved in cancer initiation, progression and metastasis. In prostate cancer, the androgen receptor (AR) protein has pivotal functions, and over the years it has been the target of different drugs. AR is a nuclear receptor whose activity is regulated by a phosphorylation mechanism controlled by hormone and growth factors. Following phosphorylation, AR interacts with many cofactors that closely control its function. Among such cofactors, Pin1 is a peptidyl-prolyl isomerase that is involved in the control of protein phosphorylation and has a prognostic value in prostate cancer. In the present study, we demonstrate that ARSer81 is involved in the interaction with Pin1, and that this interaction is important for the transcriptional activity of AR. Since Pin1 expression positively correlates with tumor grade, our results suggest that Pin1 can participate in this process by modulating AR function.
Received: June 13, 2012; Accepted: August 3, 2012; Published Online: August 16, 2012
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