"Unexpected roles of 14-3-3 scaffolds in metabolism and metabolic disease"
Dr. Gareth Lim
University of Montreal / CHUM
Complex signaling networks, consisting of receptors, kinases, and transcription factors, are involved in the regulation of metabolism, but how these events are accurately coordinated within key metabolically relevant cells, such as the fat cell, are not well known. Molecular scaffolds, such as those belonging to the 14-3-3 protein family, are ideal candidates due to their ability to facilitate protein localization and protein-protein interactions. In general, scaffold proteins are presumed to have passive signaling roles, but their ability to interact with numerous metabolic effector molecules suggest that they may actively participate in key processes that contribute to fat cell function. We recently discovered novel roles of 14-3-3 proteins, and specifically the 14-3-3ζ isoform, in the regulation of pancreatic β-cell survival, adipogenesis, and glucose homeostasis. As alterations in the activity of signaling effectors can promote the pathogenesis of chronic diseases, such as type 2 diabetes and obesity, it raises the question of whether de-regulated 14-3-3 protein function can have detrimental effects on metabolic heath. Thus, the overall objectives of my research group are aimed at exploring how 14-3-3 proteins facilitate signaling events underlying metabolism and to investigate their potential contributions to the development of chronic diseases, with a particular focus on obesity. The long-term goal is to determine if 14-3-3 proteins or components of their interactomes can one day be targeted for the treatment of obesity, which is a growing health concern in Canada and throughout the world.