PML, SUMO, and RNF4: Guardians of Nuclear Protein Quality

In this issue of Molecular Cell , Guo et al. (2014) report that misfolded or aggregated nuclear proteins, such as pathogenic polyQ proteins, are cleared by a SUMO-dependent quality control pathway, which involves the E3 SUMO ligase PML and the SUMO-targeted ubiquitin ligase RNF4.