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dc.contributor.authorGiannini, Aen_US
dc.contributor.authorMazor, Men_US
dc.contributor.authorOrme, Men_US
dc.contributor.authorVivanco, Men_US
dc.contributor.authorWaxman, Jen_US
dc.contributor.authorKypta, Ren_US
dc.date.accessioned2018-09-12T11:43:05Z
dc.date.issued2004en_US
dc.identifier1en_US
dc.identifier.citationExperimental Cell Research, 2004, 295 pp. 150 - 160en_US
dc.identifier.issn0014-4827en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2643
dc.identifier.doi10.1016/j.yexcr.2003.12.012en_US
dc.description.abstractMutations in APC or in β-catenin, which are common in colon cancer, lead to constitutive activation of β-catenin/Tcf-dependent signaling. α-Catenin is also found in some colon cancer cell nuclei, and loss of its expression correlates with increased β-catenin/Tcf transcriptional activity. Moreover, targeted expression of α-catenin in the nucleus inhibits β-catenin/Tcf-dependent transcription. Thus, an understanding of the regulation of α-catenin localization could provide insight into the control of β-catenin signaling. While the β-catenin/Tcf complex can promote nuclear import of α-catenin, the mechanism for its nuclear export is not known. We found that leptomycin B (LMB) inhibited nuclear export of GFP-α-catenin in HCT116 colon cancer cells, suggesting that α-catenin localization is regulated by CRM-1-dependent nuclear export. We identified two putative nuclear export signals in a domain of α-catenin that overlaps with the β-catenin binding domain. Using a nuclear export assay, we determined that one of these (NES1) is a weak LMB-insensitive NES, whereas the other (NES2) is strong and LMB-sensitive. Mutations in either NES reduced nuclear export of α-catenin in HCT116 cells. In addition, mutations in NES1, but not NES2, reduced binding of α-catenin to β-catenin and impaired the ability of α-catenin to repress β-catenin/Tcf-dependent transcription. Therefore, NES1 is required both for repression of β-catenin signaling and for nuclear export, while NES2 is required only for nuclear export.en_US
dc.format.extent150 - 160en_US
dc.titleNuclear export of α-catenin: overlap between nuclear export signal sequences and the β-catenin binding siteen_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1016/j.yexcr.2003.12.012en_US
rioxxterms.licenseref.startdate2004en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfExperimental Cell Researchen_US
pubs.noteskeywords: Catenin, Cytoskeleton, Leptomycin Ben_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.volume295en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorVivanco, Mariaen_US


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