Coordinated Actions Between p97 and Cullin-RING Ubiquitin Ligases for Protein Degradation

The cullin-RING ubiquitin ligases comprise the largest subfamily of ubiquitin ligases. They control ubiquitylation and degradation of a large number of protein substrates in eukaryotes. p97 is an ATPase domain-containing protein segregase. It plays essential roles in post-ubiquitylational events in the ubiquitin-proteasome pathway. Together with its cofactors, p97 collaborates with ubiquitin ligases to extract ubiquitylated substrates and deliver them to the proteasome for proteolysis. Here we review the structure, functions, and mechanisms of p97 in cellular protein degradation in coordination with its cofactors and the cullin-RING ubiquitin ligases.