Abstract:
Kinesin motors are a large family of molecular motors that walk along microtubules to fulfill many roles in intracellular transport, microtubule organization, and chromosome alignment. Kinesin-7 CENP-E (Centromere protein E) is a chromosome scaffold-associated protein that is located in the corona layer of centromeres, which participates in kinetochore-microtubule attachment, chromosome alignment, and spindle assembly checkpoint. Over the past 3 decades, CENP-E has attracted great interest as a promising new mitotic target for cancer therapy and drug development. In this review, we describe expression patterns of CENP-E in multiple tumors and highlight the functions of CENP-E in cancer cell proliferation. We summarize recent advances in structural domains, roles, and functions of CENP-E in cell division. Notably, we describe the dual functions of CENP-E in inhibiting and promoting tumorigenesis. We summarize the mechanisms by which CENP-E affects tumorigenesis through chromosome instability and spindle assembly checkpoints. Finally, we overview and summarize the CENP-E-specific inhibitors, mechanisms of drug resistances and their applications.
摘要:
驱动蛋白马达是一大家族的分子马达,它们沿着微管行走,在细胞内运输中发挥许多作用,微管组织,和染色体排列。Kinesin-7CENP-E(着丝粒蛋白E)是一种染色体支架相关蛋白,位于着丝粒的电晕层中,参与动粒-微管附着,染色体排列,和主轴装配检查点。在过去的30年里,CENP-E作为癌症治疗和药物开发的有希望的新的有丝分裂靶标引起了极大的兴趣。在这次审查中,我们描述了CENP-E在多种肿瘤中的表达模式,并强调了CENP-E在癌细胞增殖中的功能。我们总结了结构领域的最新进展,角色,和CENP-E在细胞分裂中的功能。值得注意的是,我们描述了CENP-E在抑制和促进肿瘤发生中的双重功能。我们总结了CENP-E通过染色体不稳定性和纺锤体组装检查点影响肿瘤发生的机制。最后,我们概述并总结了CENP-E特异性抑制剂,耐药机制及其应用。