Linkage-specific ubiquitination often leads to distinct cellular events. It has been difficult to
establish definitively the requirement for a particular linkage in mammalian degradation
pathways due to the inability to deplete endogenous ubiquitin while maintaining cell
viability. The E3 ubiquitin ligase inducible degrader of the LDL receptor (IDOL) targets the
low density lipoprotein receptor (LDLR) for degradation. The nature of the linkages
employed to signal lysosomal degradation of the LDLR, and to signal proteasomal …