摘要
真核细胞功能的完整性取决于分子和生化条块的分割。隔室之间大分子的运输需要特定的能量转运机制,可通过一类称为核胞浆转运蛋白进行转运,其被分为三个不同的组别(exportins,importins,和transportins)。CRM1参与许多蛋白质和RNA分子从细胞核至细胞质的转运。我们已找到CRM1与几种人类肿瘤的相关性,其在耐药性中的潜在作用,其作为靶向治疗的生物学证据。这里我们讨论不同癌症相关蛋白(肿瘤抑制基因、癌基因和酶的靶向治疗)的功能和作用机制,与CRM1的相关性,以及抑制CRM1的特异性,并与某些人类肿瘤的临床相关性。在检测CRM1抑制效果过程中,我们发现核运输的方向性和特定分子可能对细胞的病理生理学极为重要。现有的数据指出,CRM1依赖型调控蛋白核出口在人类某些恶性肿瘤中具有潜在生物学作用。今后深入研究应扩大和理清人类肿瘤病理生物学中这一机制的重要性。
关键词: 癌症,染色体区域保养1,exportin1,核输出信号,癌基因,抑癌基因。
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 and Maurizio Chiriva-Internati and Weimin Gao
Affiliation:
关键词: 癌症,染色体区域保养1,exportin1,核输出信号,癌基因,抑癌基因。
摘要: 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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Chuanwen Lu, Jose A. Figueroa, Zhongwei Liu, Venu Konala, Amardeep Aulakh, Rashmi Verma, Everardo Cobos and Maurizio Chiriva-Internati and Weimin Gao , 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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