Abstract
The integrity of eukaryotic cellular function depends on molecular and biochemical compartmentalization. The transport of macromolecules between compartments requires specific and energydriven mechanisms. It occurs through a class of transport proteins known as karyopherins, which are divided in three different groups (exportins, importins, and transportins). The ubiquitous exportin Chromosome Region Maintenance 1 (CRM1) is involved in the transport of many proteins and RNA molecules from nucleus to cytoplasm. We have reviewed the available evidence supporting the relevance of CRM1 in the biology of several human neoplasms, its potential role in drug resistance, and its promise as a therapeutic target. Here we discuss different cancer related proteins (tumor suppressor genes, oncogenes, and enzymatic therapeutic targets), their function, and their association with CRM1, as well as agents that specifically inhibit CRM1, their mechanism of action, and their clinical relevance in certain human neoplasms. The directionality of nuclear transport and the specific molecular cargo in question are of paramount importance when examining the effects that CRM1 inhibition may have on cellular pathophysiology. The available data point out the potential role of CRM1-dependent nuclear export of regulatory proteins in the biology of certain human malignancies. Further studies should expand and clarify the importance of this mechanism in the pathobiology of human neoplasia.
Keywords: Cancer, chromosome region maintenance 1, exportin 1, nuclear export signal, oncogene, tumor suppressor gene.
Current Cancer Drug Targets
Title:Nuclear Export as a Novel Therapeutic Target: The CRM1 Connection
Volume: 15 Issue: 7
Author(s): Chuanwen Lu, Jose A. Figueroa, Zhongwei Liu, Venu Konala, Amardeep Aulakh, Rashmi Verma, Everardo Cobos, Maurizio Chiriva-Internati and Weimin Gao
Affiliation:
Keywords: Cancer, chromosome region maintenance 1, exportin 1, nuclear export signal, oncogene, tumor suppressor gene.
Abstract: The integrity of eukaryotic cellular function depends on molecular and biochemical compartmentalization. The transport of macromolecules between compartments requires specific and energydriven mechanisms. It occurs through a class of transport proteins known as karyopherins, which are divided in three different groups (exportins, importins, and transportins). The ubiquitous exportin Chromosome Region Maintenance 1 (CRM1) is involved in the transport of many proteins and RNA molecules from nucleus to cytoplasm. We have reviewed the available evidence supporting the relevance of CRM1 in the biology of several human neoplasms, its potential role in drug resistance, and its promise as a therapeutic target. Here we discuss different cancer related proteins (tumor suppressor genes, oncogenes, and enzymatic therapeutic targets), their function, and their association with CRM1, as well as agents that specifically inhibit CRM1, their mechanism of action, and their clinical relevance in certain human neoplasms. The directionality of nuclear transport and the specific molecular cargo in question are of paramount importance when examining the effects that CRM1 inhibition may have on cellular pathophysiology. The available data point out the potential role of CRM1-dependent nuclear export of regulatory proteins in the biology of certain human malignancies. Further studies should expand and clarify the importance of this mechanism in the pathobiology of human neoplasia.
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Lu Chuanwen, Figueroa A. Jose, Liu Zhongwei, Konala Venu, Aulakh Amardeep, Verma Rashmi, Cobos Everardo, Chiriva-Internati Maurizio and Gao Weimin, Nuclear Export as a Novel Therapeutic Target: The CRM1 Connection, Current Cancer Drug Targets 2015; 15 (7) . https://dx.doi.org/10.2174/156800961507150828223554
DOI https://dx.doi.org/10.2174/156800961507150828223554 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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