Yang Yu-Hao, Wei Ya-Lan, She Zhen-Yu
Department of Cell Biology and Genetics, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
Key Laboratory of Stem Cell Engineering and Regenerative Medicine, Fujian Province University, Fuzhou, China.
Front Mol Biosci. 2024 Mar 15;11:1366113. doi: 10.3389/fmolb.2024.1366113. eCollection 2024.
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.
驱动蛋白是一大类分子马达，它们沿着微管移动，在细胞内运输、微管组织和染色体排列中发挥多种作用。驱动蛋白-7着丝粒蛋白E（CENP-E）是一种与染色体支架相关的蛋白质，位于着丝粒的冠层，参与动粒-微管附着、染色体排列和纺锤体组装检查点。在过去的30年里，CENP-E作为癌症治疗和药物开发的一个有前景的新的有丝分裂靶点，引起了人们极大的兴趣。在这篇综述中，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CENP-E在细胞分裂中的结构域、作用和功能的最新进展。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。
