Controlling the Gatekeeper: Therapeutic Targeting of Nuclear Transport
Nuclear transport receptors of the karyopherin superfamily of proteins transport macromolecules from one compartment to the other and are critical for both cell physiology and pathophysiology. The nuclear transport machinery is tightly regulated and essential to a number of key cellular processes si...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/7/11/221 |
| _version_ | 1827851751314685952 |
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| author | Friederike K. Kosyna Reinhard Depping |
| author_facet | Friederike K. Kosyna Reinhard Depping |
| author_sort | Friederike K. Kosyna |
| collection | DOAJ |
| description | Nuclear transport receptors of the karyopherin superfamily of proteins transport macromolecules from one compartment to the other and are critical for both cell physiology and pathophysiology. The nuclear transport machinery is tightly regulated and essential to a number of key cellular processes since the spatiotemporally expression of many proteins and the nuclear transporters themselves is crucial for cellular activities. Dysregulation of the nuclear transport machinery results in localization shifts of specific cargo proteins and associates with the pathogenesis of disease states such as cancer, inflammation, viral illness and neurodegenerative diseases. Therefore, inhibition of the nuclear transport system has future potential for therapeutic intervention and could contribute to the elucidation of disease mechanisms. In this review, we recapitulate clue findings in the pathophysiological significance of nuclear transport processes and describe the development of nuclear transport inhibitors. Finally, clinical implications and results of the first clinical trials are discussed for the most promising nuclear transport inhibitors. |
| first_indexed | 2024-03-12T10:38:13Z |
| format | Article |
| id | doaj.art-053056d7cb3741bb99ab71d19a85d293 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T10:38:13Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-053056d7cb3741bb99ab71d19a85d2932023-09-02T08:23:38ZengMDPI AGCells2073-44092018-11-0171122110.3390/cells7110221cells7110221Controlling the Gatekeeper: Therapeutic Targeting of Nuclear TransportFriederike K. Kosyna0Reinhard Depping1Institute of Physiology, Center for Structural and Cell Biology in Medicine, University of Lübeck, Ratzeburger Allee 160, D-23562 Lübeck, GermanyInstitute of Physiology, Center for Structural and Cell Biology in Medicine, University of Lübeck, Ratzeburger Allee 160, D-23562 Lübeck, GermanyNuclear transport receptors of the karyopherin superfamily of proteins transport macromolecules from one compartment to the other and are critical for both cell physiology and pathophysiology. The nuclear transport machinery is tightly regulated and essential to a number of key cellular processes since the spatiotemporally expression of many proteins and the nuclear transporters themselves is crucial for cellular activities. Dysregulation of the nuclear transport machinery results in localization shifts of specific cargo proteins and associates with the pathogenesis of disease states such as cancer, inflammation, viral illness and neurodegenerative diseases. Therefore, inhibition of the nuclear transport system has future potential for therapeutic intervention and could contribute to the elucidation of disease mechanisms. In this review, we recapitulate clue findings in the pathophysiological significance of nuclear transport processes and describe the development of nuclear transport inhibitors. Finally, clinical implications and results of the first clinical trials are discussed for the most promising nuclear transport inhibitors.https://www.mdpi.com/2073-4409/7/11/221nuclear transportexportinimportinkaryopherinchromosome region maintenance 1 (CRM1)cancerdrugnuclear transport inhibitor |
| spellingShingle | Friederike K. Kosyna Reinhard Depping Controlling the Gatekeeper: Therapeutic Targeting of Nuclear Transport Cells nuclear transport exportin importin karyopherin chromosome region maintenance 1 (CRM1) cancer drug nuclear transport inhibitor |
| title | Controlling the Gatekeeper: Therapeutic Targeting of Nuclear Transport |
| title_full | Controlling the Gatekeeper: Therapeutic Targeting of Nuclear Transport |
| title_fullStr | Controlling the Gatekeeper: Therapeutic Targeting of Nuclear Transport |
| title_full_unstemmed | Controlling the Gatekeeper: Therapeutic Targeting of Nuclear Transport |
| title_short | Controlling the Gatekeeper: Therapeutic Targeting of Nuclear Transport |
| title_sort | controlling the gatekeeper therapeutic targeting of nuclear transport |
| topic | nuclear transport exportin importin karyopherin chromosome region maintenance 1 (CRM1) cancer drug nuclear transport inhibitor |
| url | https://www.mdpi.com/2073-4409/7/11/221 |
| work_keys_str_mv | AT friederikekkosyna controllingthegatekeepertherapeutictargetingofnucleartransport AT reinharddepping controllingthegatekeepertherapeutictargetingofnucleartransport |