CHARACTERIZATION OF THE PLK4 KINASE

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 精确控制中心体的数量，主要的微管- 动物细胞的组织中心，对于维持 基因组完整性中心体数目的减少可以促进 纺锤体形成的错误导致随后的染色体 在许多癌症中发现了错误分离和额外的中心体。 中心体由一对中心粒组成， 无定形的中心粒周围物质和中心体复制， 由中心粒复制控制。Polo样激酶4（Plk 4）在细胞凋亡中起重要作用。 在启动中心粒复制和过表达中的关键作用 plk 4促进中心粒过度复制和额外的 中心体 最近，我们发现激酶活性Plk 4是 固有地不稳定并且是降解的目标。利用大众 光谱分析，我们证明Plk 4倍增自磷酸化 在24个氨基酸中磷酸降解决定子”和磷酸化 Plk 4不稳定性需要该区域内的多个位点。我们 继续研究Plk 4自动调节的不稳定性如何起作用， 自我限制Plk 4活性以防止中心体扩增 和基因组不稳定性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Accurate control of the number of centrosomes, the major microtubule- organizing centers of animal cells, is critical for the maintenance of genomic integrity. Abnormalities in centrosome number can promote errors in spindle formation that lead to subsequent chromosome missegregation and extra centrosomes are found in many cancers. Centrosomes are comprised of a pair of centrioles surrounded by amorphous pericentriolar material and centrosome duplication is controlled by centriole replication. Polo-like kinase 4 (Plk4) plays a key role in initiating centriole duplication and overexpression of Plk4 promotes centriole overduplication and the formation of extra centrosomes. Recently, we showed that kinase active Plk4 is inherently unstable and targeted for degradation. Using mass spectrometry we demonstrated that Plk4 multiply self-phosphorylates within a 24 amino-acid ?phosphodegron" and that phosphorylation of multiple sites within this region is required for Plk4 instability. We continue to investigate how Plk4 auto-regulated instability acts to self-limits Plk4 activity so as to prevent centrosome amplification and genomic instability.