Figure 4.
The Cdc48 / p97 targeting machine.
Cdc48 / p97 is an ATPase ring complex involved in a range of cellular processes. It can serve as a scaffold for the assembly of E3 and E4 ligases, deubiquitinating enzymes, and ubiquitinated substrates. The fate of a substrate may be determined by the various enzymatic activities associated with Cdc48.
A: The Ufd1-Npl4 heterodimer recruits a polyubiquitinated substrate to Cdc48. The polyubiquitin chain on the substrate is lengthened by Ufd2, which has E4 activity. The substrate is then passed from Ufd2 to the adaptor protein Rad23 (or Dsk2), which shuttles the protein to the proteasome for degradation. Figure adapted from39.
B: Cdc48-associated deubiquitinating enzymes (DUBs), such as Otu1, can trim the polyubiquitin chain on a substrate and prevent its degradation.