Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-?B Signaling Pathway

Basit Öğe Kaydı
dc.authoridCigdem, Sadik/0000-0003-3906-3992|Okuwaki, Mitsuru/0000-0003-2118-442X
dc.contributor.authorSaito, Shoko
dc.contributor.authorCigdem, Sadik
dc.contributor.authorOkuwaki, Mitsuru
dc.contributor.authorNagata, Kyosuke
dc.date.accessioned2025-10-24T18:09:24Z
dc.date.available2025-10-24T18:09:24Z
dc.date.issued2016
dc.departmentMalatya Turgut Özal Üniversitesi
dc.description.abstractNuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEK-Nup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-kappa B signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-kappa B-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, I kappa B, in the nucleus. These results suggest that SET-Nup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system.
dc.description.sponsorshipJapan Society for the Promotion of Science (JSPS) [24790309, 25291001]; Grants-in-Aid for Scientific Research [24790309, 26440021] Funding Source: KAKEN
dc.description.sponsorshipThis work, including the efforts of Shoko Saito, was funded by Japan Society for the Promotion of Science (JSPS) (24790309). This work, including the efforts of Kyosuke Nagata, was funded by Japan Society for the Promotion of Science (JSPS) (25291001).
dc.identifier.doi10.1128/MCB.00158-16
dc.identifier.endpage1835
dc.identifier.issn0270-7306
dc.identifier.issn1098-5549
dc.identifier.issue13
dc.identifier.pmid27114368
dc.identifier.scopus2-s2.0-84976448844
dc.identifier.scopusqualityQ1
dc.identifier.startpage1820
dc.identifier.urihttps://doi.org/10.1128/MCB.00158-16
dc.identifier.urihttps://hdl.handle.net/20.500.12899/3622
dc.identifier.volume36
dc.identifier.wosWOS:000377937900001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAmer Soc Microbiology
dc.relation.ispartofMolecular And Cellular Biology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20251023
dc.subjectMessenger-Rna Export; Pore Complex; Nucleocytoplasmic Transport; Set-Can; Myeloid-Leukemia; Gene-Regulation; Nucleoporin Nup214; In-Vivo; Dek-Can; Crm1
dc.titleLeukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-?B Signaling Pathway
dc.typeArticle

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu