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Investigating the Caspase Cleavage of the JunB Transcription Factor

  • Author / Creator
    Lee, Jason KH
  • The activation of caspases is an important step not only in apoptosis induction, but in cellular processes such as proliferation, differentiation, and the immune response. Here, we show that the AP-1 family transcription factor JunB is cleaved and dephosphorylated in a caspase-dependent manner in apoptotic cells. We demonstrate that JunB is cleaved directly by caspases, and identify aspartate 137 as the cleavage site. JunB cleavage separates the amino-terminal transactivation and carboxy-terminal DNA binding/dimerization domains to disrupt JunB transcriptional activity. Moreover, the carboxy-terminal cleavage fragment retains DNA binding activity, and the ability to dimerize with AP-1 proteins. This fragment interferes with full-length JunB binding to AP-1 sites and inhibits AP-1–dependent transcription. Finally, we show that the carboxy-terminal cleavage fragment impairs proliferation and promotes apoptosis when overexpressed in a T-cell lymphoma cell line. In summary, our findings reveal a novel mechanism of regulating the activity of an AP-1 family transcription factor.

  • Subjects / Keywords
  • Graduation date
    2013-06
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3CP7T
  • 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
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Department of Medical Microbiology and Immunology
  • Specialization
    • Immunology
  • Supervisor / co-supervisor and their department(s)
    • Ingham, Robert (Medical Microbiology and Immunology)
  • Examining committee members and their departments
    • Ostergaard, Hanne (Medical Microbiology and Immunology)
    • Goping, Ing Swie (Biochemistry)
    • Barry, Michele (Medical Microbiology and Immunology)
    • Smiley, James (Medical Microbiology and Immunology)