Identification and characterization of proteins involved in the regulation of centrosome duplication

点击翻译按钮获取中文摘要

The long-term objective of our research program is to understand the regulatory mechanisms underlying the biogenesis and duplication of centrosomes. Centrosomes are the major microtubule-nucleating centers in most eukaryotic cells which are important for a wide variety of biological processes, including the establishment of a mitotic spindle during cell division. Although centrosomes were identified more than a hundred years ago, a paucity of knowledge exists regarding their origins and duplication during the cell cycle. Faithful reproduction of this organelle is essential for chromosome segregation, and abnormalities in centrosome duplication could induce errors in cell division, resulting in cellular catastrophe, growth inhibition, and cell death. I previously identified a novel centrosomal factor, Cep76, with a unique function: it safeguards the fidelity of centrosome duplication by specifically limiting this process to once per cell cycle. To further delineate the intricate mechanisms by which Cep76 regulates duplication, proteomic analysis of immunoprecipitated proteins associated with Cep76 were recently performed to identify novel interacting proteins. Preliminary mass spectrometry sequencing data revealed known Cep76-interacting partners, along with proteins that are essential for centrosome duplication. In addition, two novel proteins of unknown or partially known function, Cep70 and Cep78, were isolated. We hypothesize that Cep70 and Cep78, like Cep76, are important regulators of centrosome duplication. Through two specific aims, we will decipher the biological functions of Cep70 and Cep78, delineate their precise relationship with Cep76, and characterize their protein interaction networks. These analyses will not only define the roles of Cep70 and Cep78 at the centrosome, but will also identify key protein-protein interactions required for the regulation of centrosome duplication. It is anticipated that these study results will further illuminate the molecular mechanisms underlying centrosome duplication and the role of this organelle in cell proliferation and survival.