Abstract:
Nuclear pore complexes (NPCs) regulate the entry and exit of molecules from the cell nucleus. Small molecules pass through NPCs by diffusion while large molecules enter and exit the nucleus by karyopherins, which serve as transport factors. Exportin-1 (XPO1) is a protein that is an important member of the karyopherin family and carries macromolecules from the nucleus to the cytoplasm. XPO1 is responsible for nuclear-cytoplasmic transport of protein, ribosomal RNA and certain required mRNAs for ribosomal biogenesis. Furthermore, XPO1-mediated nuclear export is associated with various types of disease, such as cancer, inflammation and viral infection. The key role of XPO1 in carcinogenesis and its potential as a therapeutic target has been demonstrated by previous studies. Clinical use of novel developed generation-specific XPO1 inhibitors and their combination with other agents to block XPO1-mediated nuclear export are a promising new treatment strategy. The aim of the present study was to explain the working mechanism of XPO1 and inhibitors that block XPO1-mediated nuclear export.
摘要:
核孔复合物(NPC)调节分子从细胞核的进出。小分子通过扩散通过NPCs,而大分子通过核动力蛋白进入和离开细胞核,作为运输因素。Exportin-1(XPO1)是一种蛋白质,它是核蛋白家族的重要成员,并将大分子从细胞核携带到细胞质。XPO1负责蛋白质的核-细胞质运输,核糖体RNA和核糖体生物发生所需的某些mRNA。此外,XPO1介导的核输出与各种类型的疾病有关,比如癌症,炎症和病毒感染。先前的研究已经证明了XPO1在癌变中的关键作用及其作为治疗靶标的潜力。新型开发的一代特异性XPO1抑制剂的临床使用及其与其他药物的组合来阻断XPO1介导的核输出是一种有前途的新治疗策略。本研究的目的是解释XPO1和阻断XPO1介导的核输出的抑制剂的工作机制。