Salicylic acid modulates its catabolic enzymes via proteasomal degradation linked to SCF-associated proximity networks.

Salicylic acid (SA) is a central regulator of plant immunity, and precise control of its levels is essential to balance defense and growth. However, the mechanisms controlling the stability and abundance of SA-catabolizing enzymes remain elusive. Here we show that the SA hydroxylases DOWNY MILDEW RESISTANT 6 (DMR6) and DMR6-LIKE OXYGENASE 1 (DLO1) are targeted for ubiquitin-proteasome-dependent degradation. SA promotes DMR6 turnover but stabilizes DLO1, linking catalytic activity and conformational dynamics to protein fate. Structural and biochemical analyses indicate that SA binding induces conformational changes in DMR6, particularly in a conserved C-terminal helix, which may contribute to its susceptibility to degradation. Proximity labeling of DMR6 and DLO1 identified a previously uncharacterized Kelch-type F-box protein, which we designate as DMR6-ASSOCIATED F-BOX 1 (DAF1), that contributes to SCF-type E3 ligase-mediated proteasomal turnover of DMR6 in planta, thereby modulating SA-mediated cell death. Complementary proximity labeling of the SCF adaptor ASK1 in Arabidopsis during Pseudomonas syringae infection uncovered remodeling of F-box networks while consistently recovering DMR6 and DLO1, highlighting their integration within immune-responsive proteolytic circuits. These findings support a self-limiting regulatory circuit in which SA simultaneously induces and destabilizes its catabolic enzymes, coupling hormone metabolism with proteasome-mediated control of immune homeostasis.