T BRUCEI NUCLEOLAR PROTEIN: MECHANISM OF LOCALIZATION

描述（改编自申请人的摘要）：寄生原生动物 布氏锥虫是非洲昏睡病的病原体， 非洲大约有5000万人处于危险之中。T.布鲁塞是一个 动质体细胞生物学研究的重要模式生物。霸王 布鲁氏菌磷蛋白Nopp 44/46定位于细胞器核仁 容纳核糖体的生物发生。Nopp 44/46的功能目前尚不清楚， 然而，其丰度和结合蛋白质和核酸的能力 暗示它在细胞核内起着支架的作用。Nopp 44/46不需要 含有可识别的核定位信号（NLS），并且没有已知的 一致的核仁靶向序列，留给我们的问题是如何 蛋白质进入细胞核并在核仁中积累。的一个目标 这一建议是为了确定Nopp 44/46负责其核武器的区域， 和核仁定位。此外，Nopp 44/46与一种新的 核仁G蛋白。虽然THNOGI在Nopp 44/46中的作用 定位或功能尚未确定，我们假设Nopp 44/46 通过与THNOGI相互作用搭便车进入细胞核。的目的 建议是进一步表征核和核仁的机制， 定位Nopp 44/46，并定义THNOGI在该定位中的作用。 建议的工作结果将扩大本地化的知识 机制，也可能提供线索，具体功能的THNOGI。

DESCRIPTION (Adapted from the Applicant's Abstract): The parasitic protozoan Trypanosoma brucei is the causative agent of African sleeping sickness from which approximately 50 million people in Africa are at risk. T. brucei is an important model organism for the study of kinetoplastid cell biology. The T. brucei phosphoprotein Nopp44/46 is localized to the nucleolus, an organelle housing ribosome biogenesis. The function of Nopp44/46 is currently unclear, however, its abundance and its ability to bind both proteins and nucleic acids hint that it works as a scaffold within the nucleolus. Nopp44/46 does not contain an identifiable nuclear localization signal (NLS) and there is no known consensus nucleolar targeting sequence, leaving us with the question as to how the protein enters the nucleus and accumulates in the nucleolus. One goal of this proposal is to define the regions of Nopp44/46 responsible for its nuclear and nucleolar localization. Additionally, Nopp44/46 interacts with a novel nucleolar G-protein, THNOGI. Although the role of THNOGI in Nopp44/46 localization or function has not been determined, we hypothesize that Nopp44/46 hitchhikes into the nucleus by interacting with THNOGI. The objective of this proposal is to further characterize the mechanism of both nuclear and nucleolar localization of Nopp44/46 and define the role of THNOGI in this localization. The results of the proposed work will expand the knowledge of localization mechanisms and may also provide clues as to specific functions of THNOGI.