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

Abstract EN

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.