A transcription-translation activation feedback circuit as a function of protein degradation, with the quality of protein mass adaptation related to the average functional load.
The balance between protein synthesis and degradation, and between active skeletal muscle cell hypertrophy and atrophy can be described as a function of protein degradation rate by a transcription-translation activation control loop. Transcription activity is presumed to be determined by the concentration of protein-specific fragments (PSF) occurring as intermediate products of protein degradation. If PSF acts as an apoinducer at the gene or operon enhancer region, formation and dissociation of PSF-enhancer complex, as a function of PSF concentration, determines the gene or operon transcription activity. The assumed regulation can be converted to a mathematical model that allows simulation of steady-state protein balance and active adaptation, according to the level of functional activity. The relationship between steady-state transcription activity and PSF concentration can be described by Michaelis-Menten or weak sigmoidicity kinetics. Similar dependency is presumed in translation activity as a function of mRNA concentration. The relationship of protein to mRNA, PSF and ribosome content, and their formation and degradation, are determined by first-order differential equations. The assumed regulation scheme may also contribute to the theory of transcription activation, and can be used to explain the mechanism determining active adaptation in living systems.
Mader
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Institute for Circulatory Research and Sports Medicine, Federal German Sports University, Cologne.
D005246:Feedback; D005786:Gene Expression Regulation; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism; D008954:Models, Biological; D009132:Muscles / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic
D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors