Elucidating the Functional Crosstalk Between Promyelocytic Leukemia Nuclear Bodies and Transcriptional Regulators

真核细胞的绝大多数遗传物质存在于细胞核中，这是一个高度区隔的细胞器。在细胞核内有各种各样的亚核室，它们不一定容纳遗传物质，但作为调节涉及遗传物质的各种核过程的重要中心。这些亚核区室的破坏可对细胞存活和增殖产生有害影响。这些亚核中心已被证明是许多蛋白质的永久或临时庇护所，其主要功能是确保遗传物质的忠实处理。尽管在过去的几十年里，人们已经发现了许多通过这些亚核中心运输的蛋白质因子，但这些因子如何相互沟通以实现其功能仍然是难以捉摸的。拟议的研究计划的长期目标是破译对它们相互作用的调节重要的分子密码。在接下来的五年里，我们建议阐明亚核中心（称为早幼粒细胞白血病核体）和转录调节因子之间的分子串扰，转录调节因子是一类帮助将遗传物质的信息转化为可翻译成蛋白质的脚本的蛋白质。从拟议的研究计划中获得的知识预计将大大提高我们对这些亚核体如何与其相关蛋白交流以调节对细胞活力和增殖重要的各种核过程的理解。我们期望我们的研究项目将为研究界提供有价值的试剂和工具，并为培养高素质人才提供平台。

The vast majority of the genetic material of the eukaryotic cell resides in the nucleus, which is a highly compartmentalized organelle. Within the nucleus are a variety of subnuclear compartments that do not necessarily harbour the genetic material but serve as important centers for regulating a variety of nuclear processes involving the genetic material. Disruption in these subnuclear compartments can have a deleterious effect on cell survival and proliferation. These subnuclear centers have been shown to serve as either permanent or temporary shelters for numerous proteins, whose primary function is to ensure the faithful processing of the genetic material. Although over the past decades much has been discovered about the protein factors trafficking through these subnuclear centers, how each of these factors communicates with each other to fulfill their function remains elusive. The long-term objective of the proposed research program aims to decipher the molecular code important for the regulation of their interaction. Over the next five years, we propose to elucidate the molecular crosstalk between a subnuclear center, known as promyelocytic leukemia nuclear bodies, and transcriptional regulators, a class of proteins that help turn the information of the genetic material into a script that can be translated into proteins. Knowledge gained from the proposed research program is expected to significantly enhance our understanding of how these subnuclear bodies communicate with their associated proteins to regulate a variety of nuclear processes important for cell viability and proliferation. We expect that our research program will generate valuable reagents and tools for the research community as well as provide a platform for training highly qualified personnel.