Figure 2

The role of ubiquilin in protein degradation in mammalian cells. Under normal conditions, when only low amounts of protein aggregates are present in cells (a), ubiquilin shuttles ubiquitylated proteins to the 26S proteasome via a UBL-dependent interaction with the Rpn10/S5a UIM domain. When cells contain larger amounts of aggregated protein (b), the proteasome becomes overloaded, leaving the ubiquilin UBL domain to interact with other cellular UIM proteins. These include Eps15, which instead promotes transport of aggregation-prone proteins to the aggresome. The figure is based on the model of Heir et al.[37].