CHARACTERIZATION OF THE PLK4 KINASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 准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 基因组的完整性。中心体数量异常可促进 导致后续染色体的纺锤体形成错误 在许多癌症中都发现了错误的分离和额外的中心体。 中心体由一对中心粒组成，中心粒被 无定形的中央周围物质和中心体重复 由中心粒复制控制。Polo-like kinase4(Plk4)在 在启动中心粒复制和过度表达中的关键作用 Plk4促进中心粒过度复制和额外 中心体。最近，我们发现了激酶活性Plk4是 与生俱来的不稳定和退化的目标。使用体量 光谱我们证明Plk4倍增自我磷酸化 在一个24个氨基酸的磷酸降解物中“和磷酸化的 Plk4不稳定需要该区域内的多个位置。我们 继续调查Plk4自动调节不稳定性如何作用于 自我限制Plk4活性以防止中心体放大 和基因组的不稳定性。

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.