title: pRb controls estrogen receptor alpha protein stability and activity.
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.
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA.
authors.forename: Isabella
authors.initials: I
authors.lastname: Caligiuri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Flavio
authors.initials: F
authors.lastname: Rizzolio
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D018345:Mice, Knockout; D055550:Protein Stability; D020239:Receptor Cross-Talk; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D016160:Retinoblastoma Protein
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