Molecular determinants of skeletal muscle mass: getting the "AKT" together.
Skeletal muscle is the most abundant tissue in the human body and its normal physiology plays a fundamental role in health and disease. During many disease states, a dramatic loss of skeletal muscle mass (atrophy) is observed. In contrast, physical exercise is capable of producing significant increases in muscle mass (hypertrophy). Maintenance of skeletal muscle mass is often viewed as the net result of the balance between two separate processes, namely protein synthesis and protein degradation. However, these two biochemical processes are not occurring independent of each other but they rather appear to be finely coordinated by a web of intricate signaling networks. Such signaling networks are in charge of executing environmental and cellular cues that will ultimate determine whether muscle proteins are synthesized or degraded. In this review, recent findings are discussed demonstrating that the AKT1/FOXOs/Atrogin-1(MAFbx)/MuRF1 signaling network plays an important role in the progression of skeletal muscle atrophy. These novel findings highlight an important mechanism that coordinates the activation of the protein synthesis machinery with the activation of a genetic program responsible for the degradation of muscle proteins during skeletal muscle atrophy.
Nader
Gustavo A
GA
Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave NW., Washington, DC 20010, USA. gnader@cnmcresearch.org
D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015444:Exercise / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000033:anatomy & histology* / Q000378:metabolism*; D009133:Muscular Atrophy / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt