Role of human Myocyte Enhancer Factor 2 (MEF2) proteins in cancer: structural insights, functional diversity, and regulatory mechanisms

The Myocyte Enhancer Factor 2 (MEF2) family of transcription factors plays a central role in regulating key cellular processes, including differentiation, proliferation, apoptosis and stress response. MEF2 activity is important for normal physiological development and tissue homeostasis, and its dysregulation has been implicated in a wide spectrum of disorders, including developmental anomalies, metabolic syndrome, neurodegenerative disease, and various cancers. The functional adaptability of MEF2 arise from its dynamic regulation by histone deacetylases (HDACs) and kinase such as calcium/calmodulin-dependent protein kinase (CaMK) and mitogen-activated protein kinase (MAPK), allowing it to act as both a transcriptional activator and repressor. Beyond its transcriptional roles, MEF2 influences inflammation, cell cycle control, and adaptive responses to cellular stress, highlighting its importance in health and disease. Despite substantial progress, the molecular mechanism of MEF2 regulation and function remains poorly understood. This review systematically analyzed recent advances, critical knowledge gap, and proposes future directions for research in the area of MEF2. Understanding MEF2 signaling could reveal new therapeutic targets and enable precision treatments for related disorders.