Biol Chem. 2013 Nov;394(11):1411-23. doi: 10.1515/hsz-2013-0184.
During the mitotic division cycle, cells pass through an extensive microtubule rearrangement process where microtubules forming the mitotic spindle apparatus are dynamically instable. Several centrosomal- and microtubule-associated proteins are involved in the regulation of microtubule dynamics and stability during mitosis. Here, we focus on members of the transforming acidic coiled coil (TACC) family of centrosomal adaptor proteins, in particular TACC3, in which their subcellular localization at the mitotic spindle apparatus is controlled by Aurora-A kinase-mediated phosphorylation. At the effector level, several TACC-binding partners have been identified and characterized in greater detail, in particular, the microtubule polymerase XMAP215/ch-TOG/CKAP5 and clathrin heavy chain (CHC). We summarize the recent progress in the molecular understanding of these TACC3 protein complexes, which are crucial for proper mitotic spindle assembly and dynamics to prevent faulty cell division and aneuploidy. In this regard, the (patho)biological role of TACC3 in development and cancer will be discussed.
在有丝分裂分裂周期中,细胞经历广泛的微管重排过程,其中构成有丝分裂纺锤体装置的微管动态不稳定。几种中心体和微管相关蛋白参与调节有丝分裂过程中的微管动力学和稳定性。在这里,我们重点介绍中心体衔接蛋白转化酸性卷曲螺旋(TACC)家族的成员,特别是 TACC3,其在有丝分裂纺锤体装置中的亚细胞定位受 Aurora-A 激酶介导的磷酸化控制。在效应物水平上,已经更详细地鉴定和表征了几个 TACC 结合伙伴,特别是微管聚合酶 XMAP215/ch-TOG/CKAP5 和笼蛋白重链 (CHC)。我们总结了这些 TACC3 蛋白复合物在分子理解方面的最新进展,这些复合物对于正确的有丝分裂纺锤体组装和动力学至关重要,以防止错误的细胞分裂和非整倍体。在这方面,将讨论 TACC3 在发育和癌症中的(病理)生物学作用。