Schematic illustrating a role for p97 in arsenic-induced degradation of PML. Exposure of cells to arsenic triggers increased SUMO modification of PML. Multiple copies of SUMO recruit the ubiquitin E3 ligase RNF4, which synthesizes ubiquitin chains on PML. K48-linked ubiquitin chains are recognized by the NPLOC4/UFD1 cofactors of the p97 segregase. P97 extracts and unfolds ubiquitinated and SUMOylated PML from PML bodies. PML is eventually degraded by the proteasome.