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dc.creatorLucchetti, C
dc.creatorCaligiuri, I
dc.creatorToffoli, G
dc.creatorGiordano, A
dc.creatorRizzolio, F
dc.date.accessioned2021-01-31T20:32:04Z
dc.date.available2021-01-31T20:32:04Z
dc.date.issued2013-02-04
dc.identifier.issn1932-6203
dc.identifier.issn1932-6203
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/5396
dc.identifier.other23390529 (pubmed)
dc.identifier.urihttp://hdl.handle.net/20.500.12613/5414
dc.description.abstractIn hormone receptor-positive breast cancers, most tumors in the early stages of development depend on the activity of the estrogen receptor and its ligand, estradiol. Anti-estrogens, such as tamoxifen, have been used as the first line of therapy for over three decades due to the fact that they elicit cell cycle arrest. Unfortunately, after an initial period, most cells become resistant to hormonal therapy. Peptidylprolyl isomerase 1 (Pin1), a protein overexpressed in many tumor types including breast, has been demonstrated to modulate ERalpha activity and is involved in resistance to hormonal therapy. Here we show a new mechanism through which CDK2 drives an ERalpha-Pin1 interaction under hormone- and growth factor-free conditions. The PI3K/AKT pathway is necessary to activate CDK2, which phosphorylates ERalphaSer294, and mediates the binding between Pin1 and ERalpha. Site-directed mutagenesis demonstrated that ERalphaSer294 is essential for Pin1-ERalpha interaction and modulates ERalpha phosphorylation on Ser118 and Ser167, dimerization and activity. These results open up new drug treatment opportunities for breast cancer patients who are resistant to anti-estrogen therapy. © 2013 Lucchetti et al.
dc.format.extente55355-e55355
dc.language.isoen
dc.relation.haspartPLoS ONE
dc.relation.isreferencedbyPublic Library of Science (PLoS)
dc.rightsCC BY
dc.subjectBinding Sites
dc.subjectBreast Neoplasms
dc.subjectCell Line, Tumor
dc.subjectCyclin-Dependent Kinase 2
dc.subjectDrug Resistance, Neoplasm
dc.subjectEstrogen Receptor alpha
dc.subjectFemale
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectHumans
dc.subjectMutagenesis, Site-Directed
dc.subjectNIMA-Interacting Peptidylprolyl Isomerase
dc.subjectPeptidylprolyl Isomerase
dc.subjectPhosphatidylinositol 3-Kinases
dc.subjectPhosphorylation
dc.subjectProtein Binding
dc.subjectSerine
dc.subjectSignal Transduction
dc.titleThe Prolyl Isomerase Pin1 Acts Synergistically with CDK2 to Regulate the Basal Activity of Estrogen Receptor α in Breast Cancer
dc.typeArticle
dc.type.genreJournal Article
dc.relation.doi10.1371/journal.pone.0055355
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.creator.orcidGiordano, Antonio|0000-0002-5959-016X
dc.date.updated2021-01-31T20:32:00Z
refterms.dateFOA2021-01-31T20:32:04Z


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