AS/IFN-induced Tax degradation involves NB-driven hyper-sumoylation. In untreated cells, Tax may be primarily SUMO1 conjugated and is mostly nuclear. Tax is rapidly turned over in NBs (upper pathway, red arrows). Treatment with AS/IFN dramatically enhances NB formation, promoting further Tax recruitment into NBs and its poly-sumoylation by SUMO2/3. SUMO2/3-conjugated Tax is poly-ubiquitinated by RNF4 and marked for degradation. SUMO-conjugated Tax can also be exported into cytoplasm, where degradation of the remaining molecules takes place (lower pathway, blue arrows).