Cell cycle regulation by the NEK family of protein kinases
Cell cycle regulation by the NEK family of protein kinases
复制标题
DOI：
10.1242/jcs.111195
复制
发表时间：
2012-10-01
影响因子：
4
通讯作者：
Bayliss, Richard
中科院分区：
文献类型：
--
作者：
Fry, Andrew M.;O'Regan, Laura;Bayliss, Richard
对丝状真菌构巢曲霉细胞分裂周期突变体的遗传筛选导致了有丝分裂进入所需的丝氨酸/苏氨酸激酶never-in-mitosis A（NIMA）的发现。自该发现以来，NIMA相关激酶或NEK已在大多数真核生物中被鉴定，包括人类，其中表达了11种名为NEK 1至NEK 11的遗传上不同的蛋白质。虽然没有证据表明人类NEK对于有丝分裂进入是必需的，但很明显，几个NEK家族成员在细胞周期控制中具有重要作用。特别是，NEK 2、NEK 6、NEK 7和NEK 9有助于建立基于微管的有丝分裂纺锤体，而NEK 1、NEK 10和NEK 11与DNA损伤反应有关。NEK在有丝分裂进程的其他方面，如染色质凝聚，核膜破裂，纺锤体组装检查点信号传导和胞质分裂中的作用也被提出。有趣的是，NEK 1和NEK 8也在纤毛中起作用，纤毛是从基体成核的微管结构。这导致了目前的假设，即NEK已经进化到协调分裂和非分裂细胞中的微管依赖性过程。在这里，我们回顾了人类NEKs的功能，特别强调那些参与细胞周期控制的家族成员，并考虑其作为癌症治疗靶点的潜力。
Genetic screens for cell division cycle mutants in the filamentous fungus Aspergillus nidulans led to the discovery of never-in-mitosis A (NIMA), a serine/threonine kinase that is required for mitotic entry. Since that discovery, NIMA-related kinases, or NEKs, have been identified in most eukaryotes, including humans where eleven genetically distinct proteins named NEK1 to NEK11 are expressed. Although there is no evidence that human NEKs are essential for mitotic entry, it is clear that several NEK family members have important roles in cell cycle control. In particular, NEK2, NEK6, NEK7 and NEK9 contribute to the establishment of the microtubule-based mitotic spindle, whereas NEK1, NEK10 and NEK11 have been implicated in the DNA damage response. Roles for NEKs in other aspects of mitotic progression, such as chromatin condensation, nuclear envelope breakdown, spindle assembly checkpoint signalling and cytokinesis have also been proposed. Interestingly, NEK1 and NEK8 also function within cilia, the microtubule-based structures that are nucleated from basal bodies. This has led to the current hypothesis that NEKs have evolved to coordinate microtubule-dependent processes in both dividing and non-dividing cells. Here, we review the functions of the human NEKs, with particular emphasis on those family members that are involved in cell cycle control, and consider their potential as therapeutic targets in cancer.