developmental stage:Present in myotubes and also in undifferentiated myoblasts. ,Domain:The beta domain , missing in a number of isoforms , is required for enhancement of transcriptional activity. ,Function:Transcriptional activator which binds specifically to the MEF2 element , 5'-YTA[AT] (4) TAR-3' , found in numerous muscle-specific , growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development , but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth , survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. Plays a critical role in the regulation of neuronal apoptosis. ,PTM:Acetylated on Lys-439 by CREBBP. Deacetylated by SIRT1. ,PTM:Phosphorylated on Ser-444 by CDK5 is required for Lys-439 sumoylation and inhibits transcriptional activity. In neurons , enhanced CDK5 activity induced by neurotoxins promotes caspase 3-mediated cleavage leading to neuron apoptosis. Phsophorylation on Ser-180 can be enhanced by EGF. ,PTM:Proteolytically cleaved in cerebellar granule neurons on several sites by caspase 7 following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation. ,PTM:Sumoylated on Lys-439 by SUMO2 but not SUMO1; which inhibits transcriptional activity and myogenic activity. Desumoylated by SENP3. ,similarity:Belongs to the MEF2 family. ,similarity:Contains 1 MADS-box domain. ,similarity:Contains 1 Mef2-type DNA-binding domain. ,subcellular location:Translocated by HDAC4 to nuclear dots. ,subunit:Forms a complex with class II HDACs in undifferentiating cells. On myogenic differentiation , HDACs are released into the cytoplasm allowing MEF2s to interact with other proteins for activation. Interacts with HDAC4 (in undifferentiating cells) ; the interaction translocates MEF2D to nuclear dots. Forms a heterodimer with MEF2A. ,
展开内容