IDENTIFYING MEIOSIS-SPECIFIC SUBSTRATES OF CLB5-CDK1

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。 构成动物或人类的细胞通常会分裂特定的次数，然后停止并具有允许它们执行特定功能的特性。一种特殊的细胞类型最终在男性体内形成精子，在女性体内形成卵细胞；这些细胞对生殖是必不可少的。一种被称为Cyclin/CDK的蛋白质复合体负责控制细胞分裂，这种复合体是细胞发育为精子或卵子的关键调节因素。细胞周期蛋白/CDK通过在细胞分裂过程中适时地改变一组特定的其他蛋白质的活性来发挥作用。Cyclin/CDK活性的丧失会导致不育，而对该复合体的不当调节可能会导致染色体损伤，从而导致唐斯综合征等出生缺陷。此外，Cyclin/CDK活性升高与侵袭性睾丸癌和卵巢癌有关。我们正在使用一个模型系统来理解Cyclin/CDK活性是如何被控制的，以及是什么影响导致其活性的缺陷。在目前的研究中，我们应用遗传和生化分析相结合的方法来确定由Cyclin/CDK控制的蛋白质谱。通过发现这种复合体如何发挥作用的细节，以及它调节的其他哪些蛋白质，我们希望能够设计合理的策略来克服某些类型的不孕症，并开发新的和特定的治疗方法来治疗睾丸和卵巢癌。

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. Cells that make up an animal or human normally divide a specific number of times before they stop and take on properties that allow them to perform specific functions. One particular cell type ultimately forms sperm in males and egg cells in females; these cells are essential for reproduction. A protein complex referred to as Cyclin/Cdk is responsible for controlling cell division and this complex is a key regulator of cells as they progress to become sperm or eggs. Cyclin/Cdk functions by modifying the activity of a specific set of other proteins at just the right time during the process of cell division. Loss of Cyclin/Cdk activity leads to infertility, and improper regulation of the complex can lead to chromosome damage resulting in birth defects such as Downs Syndrome. Additionally, elevated Cyclin/Cdk activity is associated with aggressive testicular and ovarian cancers. We are using a model system to understand how Cyclin/Cdk activity is controlled, and what influences cause defects in its activity. In the present study we are applying a combination of genetic and biochemical analysis to identify the spectrum of proteins that are controlled by Cyclin/Cdk. By discovering the details of how this complex functions, and what other proteins it regulates we hope to be able to design rational strategies to overcome some types of infertility and develop new and specific therapeutic approaches to testicular and ovarian cancers.