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JunB, Apoptosis, AP-1, ALK, Lymphoma, Caspase, ALK+ ALCL

Lee, Jason KH

Supervisor and department: Ingham, Robert Medical Microbiology and Immunology

Examining committee member and department: Ostergaard, Hanne Medical Microbiology and Immunology Goping, Ing Swie Biochemistry Smiley, James Medical Microbiology and Immunology Barry, Michele Medical Microbiology and Immunology

Department: Department of Medical Microbiology and Immunology

Specialization: Immunology

Date accepted: 2013-03-27T11:56:18Z

Graduation date: 2013-06

Degree: Master of Science

Degree level: Master's

Abstract: 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.

Language: English

DOI: doi:10.7939-R3CP7T

Rights: Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.

Autor: Lee, Jason KH



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