Figure 3.

Our present understanding of how UBL-UBA shuttling factors stimulate proteasomal degradation of client proteins. This mechanism summarizes multiple steps leading to processive degradation. Shuttling factors (Rad23A, Rad23B, Ddi2, Ubqln1, Ubqln2, and Ubqln4) facilitate the delivery of ubiquitinated proteins to proteasomes and, with their UBL domains, trigger this multistep activation mechanism, which involves stimulating the ATPases (the light green objects in the 19S particle) and opening the gates of the 20S α-subunits (the orange objects in the 20S particle) (for further discussion, see [31]).