dc.contributor.author | Arregi Vado, Igor | |
dc.contributor.author | Falces, Jorge | |
dc.contributor.author | Olazabal Herrero, Ane | |
dc.contributor.author | Alonso Mariño, Marian | |
dc.contributor.author | Taneva, Stefka G. | |
dc.contributor.author | Rodríguez Pérez, José Antonio | |
dc.contributor.author | Urbaneja Arrue, María Ángeles | |
dc.contributor.author | Bañuelos Rodríguez, Sonia | |
dc.date.accessioned | 2015-11-20T16:50:48Z | |
dc.date.available | 2015-11-20T16:50:48Z | |
dc.date.issued | 2015-06-19 | |
dc.identifier.citation | PLoS One 10(6): (2015) // e0130610 | es |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10810/16137 | |
dc.description.abstract | Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein, normally enriched in nucleoli, that performs several activities related to cell growth. NPM mutations are characteristic of a subtype of acute myeloid leukemia (AML), where mutant NPM seems to play an oncogenic role. AML-associated NPM mutants exhibit altered subcellular traffic, being aberrantly located in the cytoplasm of leukoblasts. Exacerbated export of AML variants of NPM is mediated by the nuclear export receptor CRM1, and due, in part, to a mutationally acquired novel nuclear export signal (NES). To gain insight on the molecular basis of NPM transport in physiological and pathological conditions, we have evaluated the export efficiency of NPM in cells, and present new data indicating that, in normal conditions, wild type NPM is weakly exported by CRM1. On the other hand, we have found that AML-associated NPM mutants efficiently form complexes with CRM1HA (a mutant CRM1 with higher affinity for NESs), and we have quantitatively analyzed CRM1HA interaction with the NES motifs of these mutants, using fluorescence anisotropy and isothermal titration calorimetry. We have observed that the affinity of CRM1HA for these NESs is similar, which may help to explain the transport properties of the mutants. We also describe NPM recognition by the import machinery. Our combined cellular and biophysical studies shed further light on the determinants of NPM traffic, and how it is dramatically altered by AML-related mutations. | es |
dc.description.sponsorship | This work was supported by the Spanish Ministry of Economy (grant SAF2014-57743-R to JAR and SB), the Basque Government (www.euskadi.net) Department of Industry (grant ETORTEK BioGUNE IE12-331), and the University of the Basque Country (grant IT709-13). JAR thanks support from the University of the Basque Country (UFI 11/20). SGT was an IKERBASQUE visiting senior researcher. IA is funded by Fundación Biofísica Bizkaia. | es |
dc.language.iso | eng | es |
dc.publisher | Public Library of Science | es |
dc.rights | info:eu-repo/semantics/openAccess | es |
dc.subject | exportin 1 | es |
dc.subject | nucleophosmin | es |
dc.subject | acute myeloblastic leukemia | es |
dc.subject | binding affinity | es |
dc.subject | complex formation | es |
dc.subject | controlled study | es |
dc.subject | embryo | es |
dc.subject | Escherichia coli | es |
dc.subject | gene mutation | es |
dc.subject | human cell | es |
dc.subject | in vivo study | es |
dc.subject | mutant | es |
dc.subject | nonhuman | es |
dc.subject | nuclear export signal | es |
dc.subject | protein expression | es |
dc.subject | protein motif | es |
dc.subject | protein protein interaction | es |
dc.subject | protein transport | es |
dc.subject | transport kinetics | es |
dc.subject | wild type | es |
dc.title | Leukemia-Associated Mutations in Nucleophosmin Alter Recognition by CRM1: Molecular Basis of Aberrant Transport | es |
dc.type | info:eu-repo/semantics/article | es |
dc.rights.holder | © 2015 Arregi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited | es |
dc.relation.publisherversion | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130610 | es |
dc.identifier.doi | 10.1371/journal.pone.0130610 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoes | Genética, antropología física y fisiología animal | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
dc.departamentoeu | Genetika,antropologia fisikoa eta animalien fisiologia | es_ES |
dc.subject.categoria | AGRICULTURAL AND BIOLOGICAL SCIENCES | |
dc.subject.categoria | MEDICINE | |
dc.subject.categoria | BIOCHEMISTRY AND MOLECULAR BIOLOGY | |