PML IV/ARF interaction enhances p53 SUMO-1 conjugation, activation, and senescence

Significance

Promyelocytic leukemia protein (PML) nuclear bodies (NBs) are subnuclear domains proposed to facilitate posttranslational modifications. Among NB partners, proteins are p53 and are most of the regulators. Overexpression of a single PML splice variant, PML IV, triggers p53-driven senescence. We demonstrate an interaction between PML IV C terminus and the ARF tumor suppressor. This interaction is required to promote p53 SUMOylation and subsequent stabilization. These results unexpectedly bridge three key tumor suppressors and stress the key role of PML NBs as SUMOylation factories and regulators of senescence.