MEF-2 isoforms' (A-D) roles in development and tumorigenesis.

Kiran Madugula,Ria Mulherkar,Zafar K Khan,Dip Patel,Degaulle I Chigbu,Pooja Jain,Edward W Harhaj

doi:10.18632/oncotarget.26763

Abstract

Myocyte enhancer factor (MEF)-2 plays a critical role in proliferation, differentiation, and development of various cell types in a tissue specific manner. Four isoforms of MEF-2 (A-D) differentially participate in controlling the cell fate during the developmental phases of cardiac, muscle, vascular, immune and skeletal systems. Through their associations with various cellular factors MEF-2 isoforms can trigger alterations in complex protein networks and modulate various stages of cellular differentiation, proliferation, survival and apoptosis. The role of the MEF-2 family of transcription factors in the development has been investigated in various cell types, and the evolving alterations in this family of transcription factors have resulted in a diverse and wide spectrum of disease phenotypes, ranging from cancer to infection. This review provides a comprehensive account on MEF-2 isoforms (A-D) from their respective localization, signaling, role in development and tumorigenesis as well as their association with histone deacetylases (HDACs), which can be exploited for therapeutic intervention.

Highlights

Myocyte enhancer factor (MEF)-2 is a member of the MCM+Agamous+Deficiens+Serum response factor (MADS) box group of transcription factors
Similar exercise regimens performed in mice, where muscle-type carnitine palmitoyl l1 (CPT1b) is involved in skeletal muscle mitochondrial β-oxidation, suggest binding of MEF-2A to the Cpt1b promoter, which elevates the growth of the quadricep muscles and development of skeletal muscle; binding activity was decreased with exercise training and increased expression of HDAC5 which correlates to the decrease in MEF-2A activity [178]
Due to the high-risk disease characteristics associated with MEF-2 aberrations, the outcomes of treatment are less encouraging, the diversity of disease phenotypes caused by MEF-2 family members are very peculiar and are associated to one or more isoforms, but the treatment regimens still more uncertain

Summary

Introduction

Myocyte enhancer factor (MEF)-2 is a member of the MCM+Agamous+Deficiens+Serum response factor (MADS) box group of transcription factors. MEF-2 is a transcriptional activator of the VSM phenotype www.oncotarget.com and regulated in an HDAC-dependent manner, and suppression of CaMKIIδ2 decreased the DNA binding affinity of MEF-2 and down regulation of its target genes Nur77 and MCP1n [90]. Studies have shown close correlation between p38 MAPKs, calcium-calmodulin dependent protein kinases and calcineurin signaling pathways that activate the expression of myogenesis via activating MEF2 transcription factors [112].

Results

Conclusion