Muscle atrophy that occurs when physical activity is decreased results from enhanced breakdown of muscle protein by the ubiquitin proteasome pathway, but the precise molecular mediators are unknown. Using gene expression profiling methods and subsequent analyses of knockout mice, Bodine et al. identified two muscle-specific ubiquitin ligases (enzymes that target protein substrates for proteolysis by the proteasome), called MAFbx and MuRF1, that are required for skeletal muscle atrophy. Identification of these proteins may lead to new therapies aimed at preventing the loss of muscle that often accompanies illness and aging.
S. C. Bodine, E. Latres, S. Baumhueter, V. K.-M. Lai, L. Nunez, B. A. Clarke, W. T. Poueymirou, F. J. Panaro, E. Na, K. Dharmarajan, Z.-Q. Pan, D. M. Valenzuela, T. M. DeChiara, T. N. Stitt, G. D. Yancopoulos, D. J. Glass, Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294, 1704-1708 (2001). [Abstract] [Full Text]