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dc.contributor.author Lagadari, Mariana
dc.contributor.author Zgajnar, Nadia Romina
dc.contributor.author Gallo, Luciana Ines
dc.contributor.author Galigniana, Mario Daniel
dc.date.available 2017-09-12T18:12:08Z
dc.date.issued 2016-05-17
dc.identifier.citation Lagadari, Mariana; Zgajnar, Nadia Romina; Gallo, Luciana Ines; Galigniana, Mario Daniel; Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity; Elsevier; Molecular Oncology; 10; 7; 17-5-2016; 1086-1098
dc.identifier.issn 1574-7891
dc.identifier.uri http://hdl.handle.net/11336/24041
dc.description.abstract FK506-binding proteins are members of the immunophilin family of proteins. Those immunophilins associated to the 90-kDa-heat-shock protein, Hsp90, have been proposed as potential modulators of signalling cascade factors chaperoned by Hsp90. FKBP51 and FKBP52 are the best characterized Hsp90-bound immunophilins first described associated to steroid-receptors. The reverse transcriptase subunit of telomerase, hTERT, is also an Hsp90 client-protein and is highly expressed in cancer cells, where it is required to compensate the loss of telomeric DNA after each successive cell division. Because FKBP51 is also a highly expressed protein in cancer tissues, we analyzed its potential association with hTERT·Hsp90 complexes and its possible biological role. In this study it is demonstrated that both immunophilins, FKBP51 and FKBP52, co-immunoprecipitate with hTERT. The Hsp90 inhibitor radicicol disrupts the heterocomplex and favors the partial cytoplasmic relocalization of hTERT in similar manner as the overexpression of the TPR-domain peptide of the immunophilin. While confocal microscopy images show that FKBP51 is primarily localized in mitochondria and hTERT is totally nuclear, upon the onset of oxidative stress, FKBP51 (but not FKBP52) becomes mostly nuclear colocalizing with hTERT, and longer exposure times to peroxide favors hTERT export to mitochondria. Importantly, telomerase activity of hTERT is significantly enhanced by FKBP51. These observations support the emerging role assigned to FKBP51 as antiapoptotic factor in cancer development and progression, and describe for the first time the potential role of this immunophilin favoring the clonal expansion by enhancing telomerase activity.
dc.format application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject FKBP51
dc.subject FKBP52
dc.subject Hsp90
dc.subject IMMUNOPHILIN I
dc.subject TELOMERASE
dc.subject hTERT
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Ciencias Biológicas
dc.subject.classification CIENCIAS NATURALES Y EXACTAS
dc.title Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-08-31T20:31:10Z
dc.identifier.eissn 1878-0261
dc.journal.volume 10
dc.journal.number 7
dc.journal.pagination 1086-1098
dc.journal.pais Países Bajos
dc.journal.ciudad Amsterdam
dc.description.fil Fil: Lagadari, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil Fil: Zgajnar, Nadia Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil Fil: Gallo, Luciana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.description.fil Fil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
dc.journal.title Molecular Oncology
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1574789116300369
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.molonc.2016.05.002
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/27233944/
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/pmid/27233944


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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)