Table of Contents
Journal of Theoretical Chemistry
Volume 2013, Article ID 313419, 10 pages
http://dx.doi.org/10.1155/2013/313419
Research Article

Theoretical Investigation of the D83V Mutation within the Myocyte-Specific Enhancer Factor-2 Beta and Its Role in Cancer

1Genome Sciences Centre, BC Cancer Agency, Suite 100 570 West 7th Avenue, Vancouver, BC, Canada
2Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada

Received 26 March 2013; Accepted 21 October 2013

Academic Editors: S. W. Rick and H. Verli

Copyright © 2013 Oleksandr Yakovenko et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The D83V mutation in the myocyte-specific enhancer factor-2 beta (MEF2B) gene is frequently observed in lymphomas. Surprisingly, this apparent gain-of-function mutation is within a protein that is involved in the promotion of apoptosis in B cells. To investigate the oncogenic effects of this alteration and explain its predominance over other known loss-of-function mutations of MEF2B, we propose a hypothesis that this mutation influences the dynamic folding of the C-terminal loop of the N-terminal domain of MEF2B. According to our hypothesis, the mutation allows MEF2B to bind promiscuously to a wider variety of gene promoters. A large set of molecular dynamic simulations (MD) was conducted to investigate the effects of D83V mutation in silico and support the hypothesis.