Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding

9 páginas, 7 figuras, 1 tabla

Detalles Bibliográficos
Autores: Díaz-Moreno, Irene, Hollingworth, David, Frenkiel, Thomas A., Kelly, Geoff, Martin, Stephen, Howell, Steven, García-Mayoral, M.F., Gherzi, Roberto, Briata, Paola, Ramos, Andrés
Tipo de recurso: artículo
Fecha de publicación:2009
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/33707
Acceso en línea:http://hdl.handle.net/10261/33707
Access Level:acceso abierto
Palabra clave:Phosphorylation
KH
KSRP
AU-rich element
RNA
Molecular
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repository_id_str
spelling Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 bindingDíaz-Moreno, IreneHollingworth, DavidFrenkiel, Thomas A.Kelly, GeoffMartin, StephenHowell, StevenGarcía-Mayoral, M.F.Gherzi, RobertoBriata, PaolaRamos, AndrésPhosphorylationKHKSRPAU-rich elementRNAMolecular9 páginas, 7 figuras, 1 tablaThe AU-rich element (ARE)-mediated mRNA-degradation activity of the RNA binding K-homology splicing regulator protein(KSRP) is regulated by phosphorylation of a serine within its N-terminal KH domain (KH1). In the cell, phosphorylation promotes the interaction of KSRP and 14-3-3f protein and impairs the ability of KSRP to promote the degradation of its RNA targets. Here we examine the molecular details of this mechanism. We report that phosphorylation leads to the unfolding of the structurally atypical and unstable KH1, creating a site for 14-3-3f binding. Using this site, 14-3-3f discriminates between phosphorylated and unphosphorylated KH1, driving the nuclear localization of KSRP. 14-3-3f –KH1 interaction regulates the mRNA-decay activity of KSRP by sequestering the protein in a separate functional pool. This study demonstrates how an mRNA-degradation pathway is connected to extracellular signaling networks through the reversible unfolding of a protein domain.I.D.-M. was supported by European Molecular Biology Organization (EMBO), fellowship number 240-2005. The work of R.G. is supported by a grant from the Associazione Italiana per le Ricerca sul Cancro (AIRC) and the Istituto Superiore di Sanita’ (ISS), whereas P.B. is a recipient of a Senior Scholar Consultancy Grant from American Italian Cancer Foundation (AICF). The work of R.G. and P.B. is also supported by the Italian Comitato Interministerial per le Programmazione Economica (CIPE)-2007Peer reviewedNature Publishing Group201120112009info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/33707reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1038/nsmb.1558info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/337072026-05-22T06:33:51Z
dc.title.none.fl_str_mv Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding
title Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding
spellingShingle Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding
Díaz-Moreno, Irene
Phosphorylation
KH
KSRP
AU-rich element
RNA
Molecular
title_short Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding
title_full Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding
title_fullStr Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding
title_full_unstemmed Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding
title_sort Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding
dc.creator.none.fl_str_mv Díaz-Moreno, Irene
Hollingworth, David
Frenkiel, Thomas A.
Kelly, Geoff
Martin, Stephen
Howell, Steven
García-Mayoral, M.F.
Gherzi, Roberto
Briata, Paola
Ramos, Andrés
author Díaz-Moreno, Irene
author_facet Díaz-Moreno, Irene
Hollingworth, David
Frenkiel, Thomas A.
Kelly, Geoff
Martin, Stephen
Howell, Steven
García-Mayoral, M.F.
Gherzi, Roberto
Briata, Paola
Ramos, Andrés
author_role author
author2 Hollingworth, David
Frenkiel, Thomas A.
Kelly, Geoff
Martin, Stephen
Howell, Steven
García-Mayoral, M.F.
Gherzi, Roberto
Briata, Paola
Ramos, Andrés
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Phosphorylation
KH
KSRP
AU-rich element
RNA
Molecular
topic Phosphorylation
KH
KSRP
AU-rich element
RNA
Molecular
description 9 páginas, 7 figuras, 1 tabla
publishDate 2009
dc.date.none.fl_str_mv 2009
2011
2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/33707
url http://hdl.handle.net/10261/33707
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1038/nsmb.1558
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869421799956021248
score 15,811543

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