title: Nuclear localization of the caspase-3-cleaved form of p73 in anoikis.
abstract: The transcription factor p73 is a homologue of p53 that can be expressed as pro- or anti-apoptotic isoforms. Unlike p53, p73 is rarely mutated or lost in cancers and it is found to replace defective p53 inducing apoptosis. Here, we investigated the p73 involvement in anoikis, a type of apoptosis caused by inadequate cell-matrix interactions. Breast cancer cell lines with different p53 status were treated with doxorubicin (DOX) or docetaxel (DOC) and cells detached from the extracellular matrix were analyzed. We demonstrate for the first time that DOX-induced cell detachment is associated with p73 cleavage and caspase activation, independently of the p53 status. However, we did not detect p73 cleavage or caspase activation in detached cells under DOC treatment. Overexpressing the apoptotic isoform of p73 led to cell detachment associated with p73 cleavage and caspase activation. Interestingly, p73 cleaved forms localize to the nucleus during the late phase of cell death indicating an increase in the transcriptional activity. Our study suggests that the cleavage of p73 on specific sites may release its pro-apoptotic function and contribute to cell death.
authors.affiliation: Gustave Roussy, INSERM U981, Univ Paris-Sud, F 94805 Villejuif, France.|IRCIV, Univ Paris-Sud, F 94805 Villejuif, France.
authors.forename: Samar
authors.initials: S
authors.lastname: Alsafadi
authors.affiliation: Department of Biopathology, Gustave Roussy, F 94805 Villejuif, France.|IRCIV, Univ Paris-Sud, F 94805 Villejuif, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tourpin
authors.affiliation: Gustave Roussy, INSERM U981, Univ Paris-Sud, F 94805 Villejuif, France.|IRCIV, Univ Paris-Sud, F 94805 Villejuif, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Bessoltane
authors.affiliation: Imaging and Cytometry Platform, Gustave Roussy, F 94805 Villejuif, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Salomé-Desnoulez
authors.affiliation: IRCIV, Univ Paris-Sud, F 94805 Villejuif, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Vassal
authors.affiliation: Gustave Roussy, INSERM U981, Univ Paris-Sud, F 94805 Villejuif, France.|IRCIV, Univ Paris-Sud, F 94805 Villejuif, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.affiliation: Gustave Roussy, INSERM U981, Univ Paris-Sud, F 94805 Villejuif, France.|IRCIV, Univ Paris-Sud, F 94805 Villejuif, France.|Faculté de Pharmacie, Université de Picardie Jules Vernes, 80000 Amiens, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Ahomadegbe
mesh_terms: D023102:Anoikis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D043823:Taxoids / Q000494:pharmacology; D014162:Transfection; D000072160:Tumor Protein p73 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C495901:TP53 protein, human; C000606460:TP73 protein, human; D043823:Taxoids; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D000077143:Docetaxel; D004317:Doxorubicin; D053148:Caspase 3
keywords: anoikis; cleaved p73; nuclear localization