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Less Is More: How Protein Degradation Regulates Muscle Development

  • T. Hoppe
Conference paper
Part of the Ernst Schering Foundation Symposium Proceedings book series (SCHERING FOUND, volume 2008/1)

Abstract

The organization of sarcomeric structures during muscle development involves regulated multistep assembly pathways. The myosin assembly factor UNC-45 functions both as a molecular chaperone and as an Hsp90 co-chaperone for myosin throughout muscle thick-filament formation. Consequently, mutations in unc-45 result in paralyzed worms with severe myofibril disorganization in striated body wall muscles. Our data suggest that functional muscle formation in Caenorhabditis elegans is linked to ubiquitin-dependent UNC-45 turnover, regulated by the E3 enzymes UFD-2 and CHN-1 in cooperation with the ubiquitin-selective chaperone CDC-48 (also known as p97 in human). Missense mutations in the gene encoding p97 are known to cause a dominant, late-onset hereditary inclusion body myopathy. Remarkably, we identified a conserved role of CDC-48/p97 in the process of myofiber differentiation and maintenance, which appears to have important implications for understanding defects in muscle formation and maintenance during pathological conditions.

Keywords

Muscle Development Body Wall Muscle Sarcomeric Structure Inclusion Body Myopathy Ubiquitin Moiety 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) at the Institute for GeneticsUniversity of CologneCologneGermany

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