New role for SUMO in death by UV

The small ubiquitin-like modifier (SUMO) ligase protein inhibitor of activated stat-1 (PIAS1) – one of the four mammalian PIAS proteins – is known to have a role in cellular stress response by SUMOylating several proteins that are involved in DNA repair, apoptosis and transcription. On page 5819, Raghavi Sudharsan and Yoshiaki Azuma expand upon these functions by demonstrating a previously unknown role for PIAS1 in UV-induced apoptosis. Using ectopic expression of PIAS1 in HeLa cells, they show that PIAS1 – but not the other PIAS members – induces UV-mediated apoptosis in these cells, which is mediated by the recruitment of the pro-apoptotic death-associated protein 6 (Daxx) to SUMOylated PIAS1 foci and depends on its SUMO-ligase activity. Furthermore, depletion of Daxx alleviates PIAS1-mediated UV-sensitivity. Analysing the protein domains responsible for this function, the authors show that the N-terminus of PIAS1 governs substrate specificity and regulates Daxx recruitment, and thus apoptosis, whereas recruitment of Daxx to SUMOylated foci depends on its C-terminal SUMO-interacting motif (SIM). Consequently, Daxx mutants lacking the SIM domain are unable to form SUMOylated foci and do not show an increased sensitivity to UV-irradiation in the presence of PIAS1. On the basis of these observations, the authors propose a new role for PIAS1-mediated SUMOylation in sensitising cells to UV damage through the recruitment of Daxx to PIAS1-specific SUMOylated substrates.