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Cells 2018, 7(11), 221; https://doi.org/10.3390/cells7110221

Controlling the Gatekeeper: Therapeutic Targeting of Nuclear Transport

Institute of Physiology, Center for Structural and Cell Biology in Medicine, University of Lübeck, Ratzeburger Allee 160, D-23562 Lübeck, Germany
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Received: 25 October 2018 / Revised: 16 November 2018 / Accepted: 17 November 2018 / Published: 21 November 2018
(This article belongs to the Special Issue Nuclear Transport in Ageing and Diseases)
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Abstract

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. View Full-Text
Keywords: nuclear transport; exportin; importin; karyopherin; chromosome region maintenance 1 (CRM1); cancer; drug; nuclear transport inhibitor nuclear transport; exportin; importin; karyopherin; chromosome region maintenance 1 (CRM1); cancer; drug; nuclear transport inhibitor
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Kosyna, F.K.; Depping, R. Controlling the Gatekeeper: Therapeutic Targeting of Nuclear Transport. Cells 2018, 7, 221.

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