Increased transcription of ubiquitin-proteasome system components: molecular responses associated with muscle atrophy.
Muscle atrophy is a common consequence of catabolic conditions like kidney failure, cancer, sepsis, and acute diabetes. Loss of muscle protein is due primarily to activation of the ubiquitin-proteasome proteolytic system. The proteolytic responses to catabolic signals include increased levels of mRNA that encode various components of the system. In the case of two genes, the proteasome C3 subunit and ubiquitin UbC, the higher levels of mRNA result from increased transcription but the mechanisms of transactivation differ between them. This review summaries the evidence that cachectic signals activate a program of selective transcriptional responses in muscle that frequently occurs coordinately with increased protein destruction.
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Renal Division, Emory University, Room 338, Woodruff Memorial Research Building, 1639 Pierce Drive, Atlanta, GA 30322, USA. medrp@emory.edu <medrp@emory.edu>
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009133:Muscular Atrophy / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010447:Peptide Hydrolases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism*
D005938:Glucocorticoids; D016328:NF-kappa B; D016329:Sp1 Transcription Factor; D025801:Ubiquitin; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease