Two functionally distinct E2/E3 pairs coordinate sequential ubiquitination of a common substrate in Caenorhabditis elegans development

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Abstract
Significance: Ubiquitination—the covalent attachment of ubiquitin to substrates—is a posttranslational modification that regulates virtually every aspect of cellular function in eukaryotes. The final step of substrate ubiquitination requires the coordination of two types of enzymes: ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s). Whereas E3s can function with different E2s, coordination between E3s has been reported only for E3s of the same class. Here we show that two distinct E2/E3 pairs (UBC-18/ARI-1 and UBC-3/CUL-1) coordinate to ubiquitinate a common substrate and regulate its steady-state levels in C. elegans . Failure to regulate the substrate's levels leads to a serious developmental defect and lethality in worms. Our work provides evidence that cross-talk between two classes of E3s and their respective dedicated E2s occurs in an organism.
Funding Information
  • HHS | National Institutes of Health (R01 GM088055)
  • HHS | National Institutes of Health (NRSA 5T32 GM007270)
  • HHS | National Institutes of Health (P20 GM103432)
  • HHS | National Institutes of Health (R01 GM066868)
  • HHS | National Institutes of Health (R01 AG044378)

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