Nuclear transport surveillance of p53 by nuclear pores in glioblastoma
Summary: Nuclear pore complexes (NPCs) are the central apparatus of nucleocytoplasmic transport. Disease-specific alterations of NPCs contribute to the pathogenesis of many cancers; however, the roles of NPCs in glioblastoma (GBM) are unknown. In this study, we report genomic amplification of NUP107...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723008938 |
| _version_ | 1797731105587068928 |
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| author | Dini Kurnia Ikliptikawati Nozomi Hirai Kei Makiyama Hemragul Sabit Masashi Kinoshita Koki Matsumoto Keesiang Lim Makiko Meguro-Horike Shin-ichi Horike Masaharu Hazawa Mitsutoshi Nakada Richard W. Wong |
| author_facet | Dini Kurnia Ikliptikawati Nozomi Hirai Kei Makiyama Hemragul Sabit Masashi Kinoshita Koki Matsumoto Keesiang Lim Makiko Meguro-Horike Shin-ichi Horike Masaharu Hazawa Mitsutoshi Nakada Richard W. Wong |
| author_sort | Dini Kurnia Ikliptikawati |
| collection | DOAJ |
| description | Summary: Nuclear pore complexes (NPCs) are the central apparatus of nucleocytoplasmic transport. Disease-specific alterations of NPCs contribute to the pathogenesis of many cancers; however, the roles of NPCs in glioblastoma (GBM) are unknown. In this study, we report genomic amplification of NUP107, a component of NPCs, in GBM and show that NUP107 is overexpressed simultaneously with MDM2, a critical E3 ligase that mediates p53 degradation. Depletion of NUP107 inhibits the growth of GBM cell lines through p53 protein stabilization. Mechanistically, NPCs establish a p53 degradation platform via an export pathway coupled with 26S proteasome tethering. NUP107 is the keystone for NPC assembly; the loss of NUP107 affects the integrity of the NPC structure, and thus the proportion of 26S proteasome in the vicinity of nuclear pores significantly decreases. Together, our findings establish roles of NPCs in transport surveillance and provide insights into p53 inactivation in GBM. |
| first_indexed | 2024-03-12T11:53:56Z |
| format | Article |
| id | doaj.art-abb1dbefb5d34d58aae24deb4915140c |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T11:53:56Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-abb1dbefb5d34d58aae24deb4915140c2023-08-31T05:02:02ZengElsevierCell Reports2211-12472023-08-01428112882Nuclear transport surveillance of p53 by nuclear pores in glioblastomaDini Kurnia Ikliptikawati0Nozomi Hirai1Kei Makiyama2Hemragul Sabit3Masashi Kinoshita4Koki Matsumoto5Keesiang Lim6Makiko Meguro-Horike7Shin-ichi Horike8Masaharu Hazawa9Mitsutoshi Nakada10Richard W. Wong11Cell-Bionomics Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa 9201192, Japan; Laboratory of Molecular Cell Biology, Division of Transdisciplinary Sciences, Graduate School of Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa 9201192, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 9201192, JapanDepartment of Neurosurgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 9208641, Japan; Department of Neurosurgery, Toho University Ohashi Medical Center, Tokyo 1538515, JapanLaboratory of Molecular Cell Biology, Division of Transdisciplinary Sciences, Graduate School of Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa 9201192, JapanDepartment of Neurosurgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 9208641, JapanDepartment of Neurosurgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 9208641, JapanLaboratory of Molecular Cell Biology, Division of Transdisciplinary Sciences, Graduate School of Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa 9201192, JapanWPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 9201192, JapanAdvanced Science Research Center, Institute for Gene Research, Kanazawa University, Kanazawa, Ishikawa, JapanAdvanced Science Research Center, Institute for Gene Research, Kanazawa University, Kanazawa, Ishikawa, JapanCell-Bionomics Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa 9201192, Japan; Laboratory of Molecular Cell Biology, Division of Transdisciplinary Sciences, Graduate School of Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa 9201192, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 9201192, Japan; Corresponding authorDepartment of Neurosurgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 9208641, Japan; Corresponding authorCell-Bionomics Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa 9201192, Japan; Laboratory of Molecular Cell Biology, Division of Transdisciplinary Sciences, Graduate School of Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa 9201192, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 9201192, Japan; Corresponding authorSummary: Nuclear pore complexes (NPCs) are the central apparatus of nucleocytoplasmic transport. Disease-specific alterations of NPCs contribute to the pathogenesis of many cancers; however, the roles of NPCs in glioblastoma (GBM) are unknown. In this study, we report genomic amplification of NUP107, a component of NPCs, in GBM and show that NUP107 is overexpressed simultaneously with MDM2, a critical E3 ligase that mediates p53 degradation. Depletion of NUP107 inhibits the growth of GBM cell lines through p53 protein stabilization. Mechanistically, NPCs establish a p53 degradation platform via an export pathway coupled with 26S proteasome tethering. NUP107 is the keystone for NPC assembly; the loss of NUP107 affects the integrity of the NPC structure, and thus the proportion of 26S proteasome in the vicinity of nuclear pores significantly decreases. Together, our findings establish roles of NPCs in transport surveillance and provide insights into p53 inactivation in GBM.http://www.sciencedirect.com/science/article/pii/S2211124723008938CP: CancerCP: Molecular biology |
| spellingShingle | Dini Kurnia Ikliptikawati Nozomi Hirai Kei Makiyama Hemragul Sabit Masashi Kinoshita Koki Matsumoto Keesiang Lim Makiko Meguro-Horike Shin-ichi Horike Masaharu Hazawa Mitsutoshi Nakada Richard W. Wong Nuclear transport surveillance of p53 by nuclear pores in glioblastoma Cell Reports CP: Cancer CP: Molecular biology |
| title | Nuclear transport surveillance of p53 by nuclear pores in glioblastoma |
| title_full | Nuclear transport surveillance of p53 by nuclear pores in glioblastoma |
| title_fullStr | Nuclear transport surveillance of p53 by nuclear pores in glioblastoma |
| title_full_unstemmed | Nuclear transport surveillance of p53 by nuclear pores in glioblastoma |
| title_short | Nuclear transport surveillance of p53 by nuclear pores in glioblastoma |
| title_sort | nuclear transport surveillance of p53 by nuclear pores in glioblastoma |
| topic | CP: Cancer CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723008938 |
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