Although Lys48-linked ubiquitin is the canonical signal for protein clearance by the proteasome, ‘alternative’ ubiquitin signals play critical yet poorly-characterised roles in misfolded protein clearance—especially under acute stress.
Using linkage-specific ubiquitin probes and perturbation tools, we are uncovering how these additional ubiquitin signalling events maintain proteome robustness in a range of physiologic and stressed cellular contexts.
