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Exploration of Nurr1 and beta-Catenin Interactions

  • Author(s): Gragnolati, Ariel Rebecca
  • Advisor(s): Fletterick, Robert
  • et al.
Abstract

Nurr1 is a transcription factor in the nuclear receptor family that is responsible for midbrain dopaminergic neuron development and maintenance. Unlike traditional nuclear receptor signaling regulation, Nurr1 activity is not modulated by a ligand or by coregulator protein binding to its activation function-2 site. Several mechanisms for Nurr1 regulation have been proposed, including interaction with other signaling pathways. The Wnt/beta-Catenin pathway is important for proper development of many tissues, including the midbrain. Recently it has been shown that activation of this pathway stimulates the activity of Nurr1 through the direct interaction of Nurr1 with beta-catenin. Therefore, in this study I set out to define the biophysical details of this interaction. My results show that the use of expressed domains of these proteins will be useful to further examine the Nurr1/beta-catenin interaction through crystallography and cross-linking.

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