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Inhibition of NUPR1-Karyopherin β1 Binding Increases Anticancer Drug Sensitivity

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dc.contributor.author박찬희-
dc.date.accessioned2022-11-24T00:48:57Z-
dc.date.available2022-11-24T00:48:57Z-
dc.date.issued2021-03-
dc.identifier.issn1661-6596-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/191005-
dc.description.abstractBackground: Nuclear protein-1 (NUPR1, also known as p8/Com-1) is a transcription factor involved in the regulation of cellular stress responses, including serum starvation and drug stimulation. Methods: We investigated the mechanism of NUPR1 nuclear translocation involving karyopherin β1 (KPNB1), using a single-molecule binding assay and confocal microscopy. The cellular effects associated with NUPR1-KPNB1 inhibition were investigated by gene expression profiling and cell cycle analysis. Results: The single-molecule binding assay revealed that KPNB1 bound to NUPR1 with a binding affinity of 0.75 nM and that this binding was blocked by the aminothiazole ATZ-502. Following doxorubicin-only treatment, NUPR1 was translocated to the nucleus in more than 90% and NUPR1 translocation was blocked by the ATZ-502 combination treatment in MDA-MB-231 with no change in NUPR1 expression, providing strong evidence that NUPR1 nuclear translocation was directly inhibited by the ATZ-502 treatment. Inhibition of KPNB1 and NUPR1 binding was associated with a synergistic anticancer effect (up to 19.6-fold) in various cancer cell lines. NUPR1-related genes were also downregulated following the doxorubicin-ATZ-502 combination treatment. Conclusion: Our current findings clearly demonstrate that NUPR1 translocation into the nucleus requires karyopherin β1 binding. Inhibition of the KPNB1 and NUPR1 interaction may constitute a new cancer therapeutic approach that can increase the drug efficacy while reducing the side effects.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.publisherINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.relation.isPartOfINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAcrylamides / chemistry-
dc.subject.MESHAcrylamides / pharmacology*-
dc.subject.MESHActive Transport, Cell Nucleus / drug effects-
dc.subject.MESHAntibiotics, Antineoplastic / chemistry-
dc.subject.MESHAntibiotics, Antineoplastic / pharmacology-
dc.subject.MESHBasic Helix-Loop-Helix Transcription Factors / metabolism*-
dc.subject.MESHBenzothiazoles / chemistry-
dc.subject.MESHBenzothiazoles / pharmacology*-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCell Nucleus / drug effects-
dc.subject.MESHCell Nucleus / metabolism-
dc.subject.MESHCell Survival / drug effects-
dc.subject.MESHDoxorubicin / chemistry-
dc.subject.MESHDoxorubicin / pharmacology*-
dc.subject.MESHDrug Synergism-
dc.subject.MESHHumans-
dc.subject.MESHMCF-7 Cells-
dc.subject.MESHMicroscopy, Confocal-
dc.subject.MESHMolecular Structure-
dc.subject.MESHNeoplasm Proteins / metabolism*-
dc.subject.MESHProtein Binding / drug effects-
dc.subject.MESHbeta Karyopherins / metabolism*-
dc.titleInhibition of NUPR1-Karyopherin β1 Binding Increases Anticancer Drug Sensitivity-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentResearch Institute (부설연구소)-
dc.contributor.googleauthorChanhee Park-
dc.contributor.googleauthorJiwon Oh-
dc.contributor.googleauthorWon Mo Lee-
dc.contributor.googleauthorHye Ran Koh-
dc.contributor.googleauthorUy Dong Sohn-
dc.contributor.googleauthorSeung Wook Ham-
dc.contributor.googleauthorKyungsoo Oh-
dc.identifier.doi10.3390/ijms22062794-
dc.contributor.localIdA01712-
dc.relation.journalcodeJ01133-
dc.identifier.eissn1422-0067-
dc.identifier.pmid33801927-
dc.subject.keywordKPNB1-
dc.subject.keywordNUPR1-
dc.subject.keywordcombination-
dc.subject.keyworddrug sensitivity-
dc.subject.keywordprotein binding-
dc.contributor.alternativeNamePark, Chan Hee-
dc.contributor.affiliatedAuthor박찬희-
dc.citation.volume22-
dc.citation.number6-
dc.citation.startPage2794-
dc.identifier.bibliographicCitationINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.22(6) : 2794, 2021-03-
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers

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