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Inhibition of NUPR1-Karyopherin β1 Binding Increases Anticancer Drug Sensitivity
DC Field | Value | Language |
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dc.contributor.author | 박찬희 | - |
dc.date.accessioned | 2022-11-24T00:48:57Z | - |
dc.date.available | 2022-11-24T00:48:57Z | - |
dc.date.issued | 2021-03 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/191005 | - |
dc.description.abstract | Background: 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.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.publisher | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.relation.isPartOf | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Acrylamides / chemistry | - |
dc.subject.MESH | Acrylamides / pharmacology* | - |
dc.subject.MESH | Active Transport, Cell Nucleus / drug effects | - |
dc.subject.MESH | Antibiotics, Antineoplastic / chemistry | - |
dc.subject.MESH | Antibiotics, Antineoplastic / pharmacology | - |
dc.subject.MESH | Basic Helix-Loop-Helix Transcription Factors / metabolism* | - |
dc.subject.MESH | Benzothiazoles / chemistry | - |
dc.subject.MESH | Benzothiazoles / pharmacology* | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Cell Nucleus / drug effects | - |
dc.subject.MESH | Cell Nucleus / metabolism | - |
dc.subject.MESH | Cell Survival / drug effects | - |
dc.subject.MESH | Doxorubicin / chemistry | - |
dc.subject.MESH | Doxorubicin / pharmacology* | - |
dc.subject.MESH | Drug Synergism | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | MCF-7 Cells | - |
dc.subject.MESH | Microscopy, Confocal | - |
dc.subject.MESH | Molecular Structure | - |
dc.subject.MESH | Neoplasm Proteins / metabolism* | - |
dc.subject.MESH | Protein Binding / drug effects | - |
dc.subject.MESH | beta Karyopherins / metabolism* | - |
dc.title | Inhibition of NUPR1-Karyopherin β1 Binding Increases Anticancer Drug Sensitivity | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Research Institute (부설연구소) | - |
dc.contributor.googleauthor | Chanhee Park | - |
dc.contributor.googleauthor | Jiwon Oh | - |
dc.contributor.googleauthor | Won Mo Lee | - |
dc.contributor.googleauthor | Hye Ran Koh | - |
dc.contributor.googleauthor | Uy Dong Sohn | - |
dc.contributor.googleauthor | Seung Wook Ham | - |
dc.contributor.googleauthor | Kyungsoo Oh | - |
dc.identifier.doi | 10.3390/ijms22062794 | - |
dc.contributor.localId | A01712 | - |
dc.relation.journalcode | J01133 | - |
dc.identifier.eissn | 1422-0067 | - |
dc.identifier.pmid | 33801927 | - |
dc.subject.keyword | KPNB1 | - |
dc.subject.keyword | NUPR1 | - |
dc.subject.keyword | combination | - |
dc.subject.keyword | drug sensitivity | - |
dc.subject.keyword | protein binding | - |
dc.contributor.alternativeName | Park, Chan Hee | - |
dc.contributor.affiliatedAuthor | 박찬희 | - |
dc.citation.volume | 22 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 2794 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.22(6) : 2794, 2021-03 | - |
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