In this issue, Jaffray and colleagues (https://doi.org/10.1083/jcb.202407133) detail the molecular machinery required to degrade the oncogene PML in response to arsenic treatment. Different posttranslational modifiers team up: ubiquitin, SUMO1, and -2/3, linked by the SUMO-targeted ubiquitin ligases TOPORS and RNF4.
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