During the immune response, the Arabidopsis U-box-type E3 ligase PUB22 was shown to negatively regulate immune signalling by targeting components of the vesicular trafficking. However, little is known about the molecular mechanisms controlling its activity. Here, I show that PUB22 is regulated via ubiquitination, which determines its continuous degradation. However, upon activation of the immune response PUB22 is stabilized by MPK3-mediated phosphorylation. Mimicking phosphorylation resulted in increased stability of PUB22 in vivo, correlating with a reduced autoubiquitination activity in vitro. Autoubiquitination is dependent on the oligomerization of PUB22, which is inhibited by phosphorylation. I propose a model in which MPK3-mediated phosphorylation of PUB22 determines an activity switch by disrupting oligomerization, rescuing PUB22 from degradation and allowing it to engage targets to dampen cellular signalling during immunity. The importance of PUB22 phosphorylation is shown by complementation analysis, demonstrating that phosphomimetic mutants, however not phosphonull mutants, efficiently dampen the immune response.