Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4-multiubiquitylation complex in C. elegans

Cell. 2004 Aug 6;118(3):337-49. doi: 10.1016/j.cell.2004.07.014.


The organization of the motor protein myosin into motile cellular structures requires precise temporal and spatial control. Caenorhabditis elegans UNC-45 facilitates this by functioning both as a chaperone and as a Hsp90 cochaperone for myosin during thick filament assembly. Consequently, mutations in C. elegans unc-45 result in paralyzed animals with severe myofibril disorganization in striated body wall muscles. Here, we report a new E3/E4 complex, formed by CHN-1, the C. elegans ortholog of CHIP (carboxyl terminus of Hsc70-interacting protein), and UFD-2, an enzyme known to have ubiquitin conjugating E4 activity in yeast, as necessary and sufficient to multiubiquitylate UNC-45 in vitro. The phenotype of unc-45 temperature-sensitive animals is partially suppressed by chn-1 loss of function, while UNC-45 overexpression in worms deficient for chn-1 results in severely disorganized muscle cells. These results identify CHN-1 and UFD-2 as a functional E3/E4 complex and UNC-45 as its physiologically relevant substrate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Mutation
  • Myosins / metabolism
  • Temperature
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*


  • Caenorhabditis elegans Proteins
  • Molecular Chaperones
  • unc-45 protein, C elegans
  • Ubiquitin-Conjugating Enzymes
  • let-70 protein, C elegans
  • Ubiquitin-Protein Ligases
  • Myosins