Polo-like kinase 1 (PLK1) dynamically changes its localization and plays important roles in proper mitotic progression. In particular, strict control of cytoplasmic PLK1 is needed to prevent mitotic defects. However, the regulation of cytoplasmic PLK1 is not fully understood. In this study, we show that CEP76, a centriolar protein, physically interacts with PLK1 and tightly controls the activation of cytoplasmic PLK1 during mitosis in human cells. We found that removal of centrosomes induced ectopic aggregation of PLK1, which is highly phosphorylated, in the cytoplasm during mitosis. Importantly, a targeted RNAi screen revealed that depletion of CEP76 resulted in a similar phenotype. In addition, depletion of CEP76 caused defective spindle orientation and mitotic delay. Moreover, the formation of ectopic PLK1 aggregates and defective spindle orientation were significantly suppressed by the inhibition of PLK1 kinase activity. Overall, these results demonstrate that CEP76 suppresses the aberrant activation of cytoplasmic PLK1 for proper mitotic progression.

This article has an associated First Person interview with the first author of the paper.

Polo 样激酶 1 (PLK1) 动态地改变其定位，并在正常的有丝分裂进展中发挥重要作用。特别是，需要严格控制细胞质 PLK1 以防止有丝分裂缺陷。然而，细胞质PLK1的调控尚不完全清楚。在这项研究中，我们发现 CEP76（一种中心粒蛋白）与 PLK1 发生物理相互作用，并在人类细胞有丝分裂过程中严格控制细胞质 PLK1 的激活。我们发现，在有丝分裂过程中，中心体的去除会导致细胞质中高度磷酸化的 PLK1 异位聚集。重要的是，靶向 RNAi 筛选显示 CEP76 的缺失会导致类似的表型。此外，CEP76 的缺失会导致纺锤体定向缺陷和有丝分裂延迟。此外，PLK1激酶活性的抑制显着抑制了异位PLK1聚集体的形成和纺锤体方向缺陷。总体而言，这些结果表明 CEP76 抑制细胞质 PLK1 的异常激活，以实现正常的有丝分裂进展。

本文有对该论文第一作者的相关第一人称采访。