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HSP70 is required for the proper assembly of pericentriolar material and function of mitotic centrosomes.
Cell Division ( IF 2.8 ) Pub Date : 2019-05-10 , DOI: 10.1186/s13008-019-0047-7
Chieh-Ting Fang , Hsiao-Hui Kuo , Shao-Chun Hsu , Ling-Huei Yih

Background At the onset of mitosis, the centrosome expands and matures, acquiring enhanced activities for microtubule nucleation and assembly of a functional bipolar mitotic spindle. However, the mechanisms that regulate centrosome expansion and maturation are largely unknown. Previously, we demonstrated in an immortalized human cell line CGL2 and cancer cell line HeLa that the inducible form of heat shock protein 70 (HSP70) accumulates at the mitotic centrosome and is required for centrosome maturation and bipolar spindle assembly. Results In this study, we further show that HSP70 accumulated at the spindle pole in a PLK1-dependent manner. HSP70 colocalized with pericentrin (PCNT), CEP215 and γ-tubulin at the spindle pole and was required for the 3D assembly of these three proteins, which supports mitotic centrosome function. Loss of HSP70 disrupted mitotic centrosome structure, reduced pericentriolar material recruitment and induced fragmentation of spindle poles. In addition, HSP70 was necessary for the interaction between PCNT and CEP215 and also facilitated PLK1 accumulation and function at the spindle pole. Furthermore, we found that HSP70 chaperone activity is required for PCNT accumulation at the mitotic centrosome and assembly of mitotic spindles. Conclusion Our current results demonstrate that HSP70 is required for the accurate assembly of the pericentriolar material and proper functioning of mitotic centrosomes.

中文翻译:

HSP70 是中心体周围物质的正确组装和有丝分裂中心体功能所必需的。

背景在有丝分裂开始时,中心体扩张并成熟,获得增强的微管成核和组装功能性双极有丝分裂纺锤体的活性。然而,调节中心体扩张和成熟的机制在很大程度上是未知的。以前,我们在永生化人类细胞系 CGL2 和癌细胞系 HeLa 中证明,可诱导形式的热休克蛋白 70 (HSP70) 在有丝分裂中心体积累,是中心体成熟和双极纺锤体组装所必需的。结果在这项研究中,我们进一步表明HSP70 以PLK1 依赖的方式在纺锤体极积累。HSP70 与pericentrin (PCNT)、CEP215 和 γ-微管蛋白在纺锤体极共定位,是这三种蛋白质 3D 组装所必需的,它支持有丝分裂中心体功能。HSP70 的缺失破坏了有丝分裂中心体结构,减少了中心粒周围物质的募集,并诱导了纺锤体极的碎裂。此外,HSP70 是 PCNT 和 CEP215 相互作用所必需的,并且还促进了 PLK1 在主轴极的积累和功能。此外,我们发现 PCNT 在有丝分裂中心体的积累和有丝分裂纺锤体的组装需要 HSP70 伴侣活性。结论 我们目前的结果表明,HSP70 是中心粒周围材料的准确组装和有丝分裂中心体的正常运作所必需的。HSP70 是 PCNT 和 CEP215 相互作用所必需的,并且还促进了 PLK1 在主轴极的积累和功能。此外,我们发现 PCNT 在有丝分裂中心体的积累和有丝分裂纺锤体的组装需要 HSP70 伴侣活性。结论 我们目前的结果表明,HSP70 是中心粒周围材料的准确组装和有丝分裂中心体的正常运作所必需的。HSP70 是 PCNT 和 CEP215 相互作用所必需的,并且还促进了 PLK1 在主轴极的积累和功能。此外,我们发现 PCNT 在有丝分裂中心体的积累和有丝分裂纺锤体的组装需要 HSP70 伴侣活性。结论 我们目前的结果表明,HSP70 是中心粒周围材料的准确组装和有丝分裂中心体的正常运作所必需的。
更新日期:2020-04-22
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