Breast cancer gene 1 (BRCA1) contributes to the regulation of centrosome number. We previously identified receptor for activated C kinase 1 (RACK1) as a BRCA1-interacting partner. RACK1, a scaffold protein that interacts with multiple proteins through its seven WD40 domains, directly binds to BRCA1 and localizes to centrosomes. RACK1 knockdown suppresses centriole duplication, whereas RACK1 overexpression causes centriole overduplication in a subset of mammary gland-derived cells. In this study, we showed that RACK1 binds directly to polo-like kinase 1 (PLK1) and Aurora A, and promotes the Aurora A–PLK1 interaction. RACK1 knockdown decreased phosphorylated PLK1 (p-PLK1) levels and the centrosomal localization of Aurora A and p-PLK1 in S phase, whereas RACK1 overexpression increased p-PLK1 level and the centrosomal localization of Aurora A and p-PLK1 in interphase, resulting in an increase of cells with abnormal centriole disengagement. Overexpression of cancer-derived RACK1 variants failed to enhance the Aurora A–PLK1 interaction, PLK1 phosphorylation and the centrosomal localization of p-PLK1. These results suggest that RACK1 functions as a scaffold protein that promotes the activation of PLK1 by Aurora A in order to promote centriole duplication.

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乳腺癌基因 1 (BRCA1) 有助于调节中心体数量。我们之前将激活的 C 激酶 1 (RACK1) 受体鉴定为 BRCA1 相互作用伙伴。RACK1 是一种支架蛋白，通过其七个 WD40 结构域与多种蛋白相互作用，直接与 BRCA1 结合并定位于中心体。RACK1 敲除抑制中心粒复制，而 RACK1 过表达导致乳腺来源细胞子集中中心粒过度复制。在这项研究中，我们发现 RACK1 直接与 polo 样激酶 1 (PLK1) 和 Aurora A 结合，并促进 Aurora A-PLK1 相互作用。RACK1敲低降低了磷酸化PLK1（p-PLK1）水平以及Aurora A和p-PLK1在S期的中心体定位，而RACK1过表达增加了p-PLK1水平以及Aurora A和p-PLK1在间期的中心体定位，从而导致中心粒脱离异常的细胞增加。癌症来源的 RACK1 变体的过度表达未能增强 Aurora A-PLK1 相互作用、PLK1 磷酸化和 p-PLK1 的中心体定位。这些结果表明，RACK1 作为支架蛋白发挥作用，促进 Aurora A 激活 PLK1，从而促进中心粒复制。

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