CHARACTERIZATION OF THE PLK4 KINASE

PLK4 激酶的表征

• 批准号: 8171423
• 负责人: Don W Cleveland
• 金额: $ 0.24万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171423
• 关键词: Amino Acids; Animals; Cells; Centrioles; Centrosome; Chromosomes; Computer Retrieval of Information on Scientific Projects Database; Funding; Genomic Instability; Genomics; Grant; Institution; Lead; Maintenance; Malignant Neoplasms; Mass Spectrum Analysis; Microtubule-Organizing Center; Phosphorylation; Phosphotransferases; Play; Research; Research Personnel; Resources; Role; Site; Source; United States National Institutes of Health; human PLK1 protein; overexpression; prevent

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 准确控制中心体的数量，主要微管 动物细胞的组织中心对于维持至关重要 基因组完整性。中心数异常可以促进 纺锤体形成的错误，导致随后的染色体 在许多癌症中都发现了错误分析和额外的中心体。 中心体由一对环绕的中心元素组成 无定形的周围三元素材料和中心体重复是 由中心复制控制。 polo样激酶4（PLK4）播放A 在发起Centriole重复和过表达中的关键作用 PLK4促进了中心的过度填充和额外的形成 中心体。 最近，我们表明激酶活性PLK4是 本质上不稳定和降解。使用质量 光谱法我们证明了PLK4倍增自磷酸化 在24个氨基酸的磷光drophodegron中”和那种磷酸化 PLK4不稳定性需要该区域内的多个站点。我们 继续研究PLK4自动调节的不稳定性如何 自由度PLK4活性以防止中心体扩增 和基因组不稳定性。