Multiubiquitylation Pathways Involved in Muscle Assembly

• Applicant: Professor Dr. Thorsten Hoppe
• Subject Area: Developmental Biology
• Term: from 2005 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 18857872

The ubiquitin/proteasome system is pivotal for the elimination of misfolded proteins, and defects in this pathway can result in the pathogenesis of diseases such as skeletal muscle atrophy. Besides the already known E1, E2 and E3 enzymes, which are catalysts for substrate ubiquitylation, additional multiubiquitin chain elongation factors have been identified and named E4. Our recent work revealed a novel functional interaction between the Caenorhabditis elegans orthologs of the E4 enzymes CHIP and UFD2, CHN-1 and UFD-2, respectively. The E3/E4- multiubiquitylation complex formed by CHN-1 and UFD-2 regulates the stability of the myosin specific chaperone UNC-45. The central objective of our proposed research is to define the mechanism by which UFD-2/CHN-1 complex formation ensures multiubiquitylation of UNC-45 and how this is linked to myosin assembly into striated muscles.

• DFG Programme: Research Grants