Novel molecules and pathways that modulate adipogenesis

转录因子PPARgamma是核受体超家族的成员，是脂肪形成的关键调节因子。已经证明，pparγ的配体激活导致参与脂肪分化和胰岛素致敏的基因激活。尽管PPARgamma吗?自1994年以来，人们对该转录因子在配体结合时激活转录的能力进行了广泛的研究，但其与配体无关的功能尚未完全阐明。实验室的目标之一是鉴定新的分子和途径，可以调节这种转录因子的不依赖配体的活性。

The transcription factor PPARgamma, a member of the nuclear receptor superfamily, is a key regulator of adipogenesis. It has been demonstrated that ligand activation of PPARgamma leads to activation of genes involved in fat differentiation and insulin sensitization. Although PPARgamma?s ability to activate transcription upon ligand binding has been studied extensively since 1994, the ligand-independent function of this transcription factor has not been fully elucidated. One of the goals of the lab is the identification of novel molecules and pathways that can modulate the ligand-independent activity of this transcription factor. We are currently taking different approaches to study how PPARgamma is regulated and how it functions in the absence of ligand. 1)We are interested in the identification of specific cofactors that are able to bind to PPARgamma and modify its transcriptional activity in a ligand-independent manner. For this purpose, we are in the process of generating PPARgamma ?GST fusion constructs expressing different domains of PPARgamma. These constructs will be utilized in biochemical assays to potentially purify novel cofactors, from nuclear extracts of preadipocytes and fully differentiated adipocytes, that are able to interact with unliganded PPARgamma. 2) We are currently determining whether various signaling pathways can alter PPARgamma function independently of the presence of ligand. We are assessing the ability of a number of kinases to directly phosphorylate PPARgamma and its coactivators and potentially alter their adipogenic capacity. We are in the process of setting up in vitro kinase assays coupled to transient transfection and differentiation assays to determine the ability of these candidate kinases to directly influence the basal PPARgamma transcriptional activity in the absence of ligand.