Investigation of the Prader-Willi syndrome protein MAGEL2 in the regulation of Forkhead box transcription factor FOXO1

  • Author / Creator
    Devos, Julia J
  • Prader-Willi syndrome (PWS), a genetic disorder resulting from the loss of expression of multiple genes including MAGEL2, is characterized by hyperphagia and childhood-onset obesity. These symptoms point to dysfunction in the regulation of energy homeostasis. Magel2 is highly expressed in the hypothalamus, the body’s main regulator of energy balance. As the Forkhead box transcription factor FOXO1 functions in the hypothalamus to regulate food intake and body weight, I hypothesized that MAGEL2 may be involved in energy homeostasis by regulating FOXO1. Although no interaction was detected between these two proteins, I determined that MAGEL2 alters FOXO1 subcellular localization in a manner dependent upon post-translational modifications of FOXO1. Expression of MAGEL2 increases cytoplasmic localization of acetylated and phosphorylated FOXO1 and increases nuclear localization of deaceteylated FOXO1 in immunofluorescence experiments. The loss of MAGEL2 expression in PWS may impair proper FOXO1 regulation, reducing the ability of the hypothalamus to maintain energy homeostasis.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Medical Sciences-Medical Genetics
  • Supervisor / co-supervisor and their department(s)
    • Wevrick, Rachel (Medical Genetics)
  • Examining committee members and their departments
    • McDermid, Heather (Biological Sciences/Medical Genetics)
    • Berry, Fred (Surgery/Medical Genetics)
    • Haqq, Andrea (Pediatrics)
    • Wevrick, Rachel (Medical Genetics)