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dc.contributor.author Galigniana, Mario Daniel
dc.contributor.author Harrell, Jennifer M.
dc.contributor.author O´Hagen, Heather M.
dc.contributor.author Ljungman, Mats
dc.contributor.author Pratt, William B.
dc.date.available 2017-11-25T11:30:00Z
dc.date.issued 2004
dc.identifier.citation Galigniana, Mario Daniel; Harrell, Jennifer M. ; O´Hagen, Heather M. ; Ljungman, Mats ; Pratt, William B. ; Hsp90-binding immunophilins link p53 to dynein during p53 transport to the nucleus; American Society for Biochemistry and Molecular Biology; Journal Of Biological Chemistry (online); 279; 21; -1-2004; 22483-22489
dc.identifier.issn 0021-9258
dc.identifier.uri http://hdl.handle.net/11336/29103
dc.description.abstract The tumor suppressor protein p53 is known to be transported to the nucleus along microtubular tracks by cytoplasmic dynein. However, the connection between p53 and the dynein motor protein complex has not been established. Here, we show that hsp90.binding immunophilins link p53.hsp90 complexes to dynein and that prevention of that linkage in vivo inhibits the nuclear movement of p53. First, we show that p53.hsp90 heterocomplexes from DLD-1 human colon cancer cells contain an immunophilin (FKBP52, CyP-40, or PP5) as well as dynein. p53.hsp90.immunophilin.dynein complexes can be formed by incubating immunopurified p53 with rabbit reticulocyte lysate, and we show by peptide competition that the immunophilins link via their tetratricopeptide repeat domains to p53-bound hsp90 and by means of their PPIase domains to the dynein complex. The linkage of immunophilins to the dynein motor is indirect by means of the dynamitin component of the dynein-associated dynactin complex, and we show that purified FKBP52 binds directly by means of its PPIase domain to purified dynamitin. By using a temperature-sensitive mutant of p53 where cytoplasmic-nuclear movement occurs by shift to permissive temperature, we show that p53 movement is impeded when p53 binding to hsp90 is inhibited by the hsp90 inhibitor radicicol. Also, nuclear movement of p53 is inhibited when immunophilin binding to dynein is competed for by expression of a PPIase domain fragment in the same manner as when dynein linkage to cargo is dissociated by expression of dynamitin. This is the first demonstration of the linkage between an hsp90-chaperoned transcription factor and the system for its retrograde movement to the nucleus both in vitro and in vivo.
dc.format application/pdf
dc.language.iso eng
dc.publisher American Society for Biochemistry and Molecular Biology
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject CELL NUCLEUS
dc.subject HSP 90
dc.subject PROTEIN STRUCTURE
dc.subject IMMUNOPHILINS
dc.subject TUMOR SUPPRESSOR PROTEIN p53
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Ciencias Biológicas
dc.subject.classification CIENCIAS NATURALES Y EXACTAS
dc.title Hsp90-binding immunophilins link p53 to dynein during p53 transport to the nucleus
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-11-16T15:12:20Z
dc.journal.volume 279
dc.journal.number 21
dc.journal.pagination 22483-22489
dc.journal.pais Estados Unidos
dc.journal.ciudad Baltimore
dc.description.fil Fil: Galigniana, Mario Daniel. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
dc.description.fil Fil: Harrell, Jennifer M.. University of Michigan; Estados Unidos
dc.description.fil Fil: O´Hagen, Heather M.. University of Michigan; Estados Unidos
dc.description.fil Fil: Ljungman, Mats. University of Michigan; Estados Unidos
dc.description.fil Fil: Pratt, William B.. University of Michigan; Estados Unidos
dc.journal.title Journal Of Biological Chemistry (online)
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/279/21/22483.long
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1074/jbc.M402223200


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  • Articulos(IBYME) [1050]
    Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)

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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)