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

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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.