Role of transcription factors in skeletal muscle and the potential for pharmacological manipulation.
Our understanding of the role of transcription factors in skeletal muscle vastly exceeds our ability to manipulate this class of proteins for therapeutic benefit. Transcription factors responsible for controlling the fate, growth, migration, proliferation, differentiation and regeneration of muscle cells have been identified, and additional factors involved in these processes continue to be discovered. These factors are often involved in multiple steps in muscle differentiation and can have redundant activities. As such, a detailed understanding of their intermolecular interactions and the gene programs they control is essential to the rational design of therapeutics. Mutations in transcription factors cause a number of muscle disorders. Moreover, the manipulation of transcriptional signals holds the promise of treating muscle diseases by exploiting the ability of muscle cells to regenerate after injury. Finally, several proteins have recently been shown to inhibit muscular dystrophy in mouse models. Because some of these proteins are enriched at the neuromuscular synapse, the manipulation of factors governing synaptic transcription is a promising new approach to the treatment of muscular dystrophy.
Martin
Paul T
PT
Department of Neuroscience, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0691, USA. pmartin@ucsd.edu
D000123:Acetyltransferases / Q000235:genetics / Q000502:physiology; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D015195:Drug Design; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D064326:MEF2 Transcription Factors; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009136:Muscular Dystrophies / Q000188:drug therapy / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000235:genetics; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C068686:Pax3 protein, mouse; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases