Cell biology. An ancient portal to proteolysis

Abstract

The discovery in archaea of an alternative proteasome based on Cdc48 provides insights into theevolution of protein degradation machines.

Figure. Two models of eukaryotic Cdc48 action

(A) In model 1, Cdc48 has lost its ancient ability to interact directly with the core particle and functions as an accessory factor to deliver substrates to the 26S proteasome, which contains its own 19S caps. Cdc48 can disassemble protein complexes and serve as a ubiquitin editing platform. (B) In model 2, Cdc48 retains its ability to associate with the proteasome core particle, and this allows two types of activated proteasome complexes with distinct ATPase caps to form. The different caps may be optimized for different subsets of proteasome substrates. Substrate interaction with the two proteasome particles in both models can be mediated by adaptors, which are not shown in the figure.