Regulation of cardiac myocyte cell death and differentiation by myocardin

Joseph W. Gordon

Myocardin is a cardiac- and smooth muscle-enriched transcriptional co-activator that was originally described as an interacting partner of the serum response factor. Shortly after myocardin's discovery, a wealth of published literature described the role of myocardin as a regulator of smooth muscle differentiation and phenotype modulation, while gene-targeting studies confirmed the essential role of myocardin in vascular development. More recently, myocardin has been implicated as an important regulator of cardiac myocyte differentiation in studies demonstrating direct programming of fibroblasts towards the cardiac lineage. This function of myocardin has been attributed to its physical interaction with cardiac-enriched transcription factors such as MEF2C, GATA4, and TBX5. Moreover, conditional knockout models have revealed a critical role for myocardin during cardiac chamber maturation, and a surprising function for myocardin in the regulation of cardiomyocyte proliferation, cell death, and possibly mitochondrial function. This review summarizes the literature surrounding the cardiac-specific roles of myocardin during development and post-natal cardiac remodeling. In addition, we take a bioinformatics and computational approach to discuss known and predicted interactions and biological functions of myocardin, which suggests areas for future research.