FIGURE 7.

Model for Lys⁶³-specific DUB regulation in different cellular compartments. The BRISC and BRCA1-RAP80 complexes are differentially regulated by protein-protein interactions in the cytoplasm and nucleus, respectively. Formation of each complex is limited in part by the abundance of the other complex. In the nucleus, the ubiquitin binding of RAP80 targets the RAP80 complex to DSBs. We theorize that the same mechanism exists in the cytoplasm, where an unknown protein targets DUB activity within the BRISC to act on yet to be identified K63-Ub targets.