Oncotarget

Research Papers:

pRb controls Estrogen Receptor alpha protein stability and activity

Isabella Caligiuri, Giuseppe Toffoli, Antonio Giordano _ and Flavio Rizzolio

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Oncotarget. 2013; 4:875-883. https://doi.org/10.18632/oncotarget.1036

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Abstract

Isabella Caligiuri1,2,3, Giuseppe Toffoli3, Antonio Giordano1,2, and Flavio Rizzolio1,3

1 Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA

2 Department of Medicine, Surgery and Neuroscience, University of Siena, Siena Italy

3 Division of Experimental and Clinical Pharmacology, Department of Molecular Biology and Translational Research, National Cancer Institute and Center for Molecular Biomedicine, Aviano (PN)

Correspondence:

Antonio Giordano , email:

Flavio Rizzolio, email:

Keywords: pRb, Estrogen receptor alpha, proteasome, chaperone proteins, breast cancer

Received: May 15, 2013, Accepted: May 31, 2013, Published: June 3, 2013

Abstract

A cross talk between the Estrogen Receptor (ESR1) and the Retinoblastoma (pRb) pathway has been demonstrated to influence the therapeutic response of breast cancer patients but the full mechanism remains poorly understood. Here we show that the N-terminal domain of pRb interacts with the CD domain of ESR1 to allow for the assembly of intermediate complex chaperone proteins HSP90 and p23. We demonstrated that a loss of pRb in human/mouse breast cells decreases the expression of the ESR1 protein through the proteasome pathway. Our work reveals a novel regulatory mechanism of ESR1 basal turnover and activity and an unanticipated relationship with the pRb tumor suppressor.


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