Pharmacological blockade of p65 palmitoylation modulates NF-κB transcriptional activity.

Inhibiting p65 autopalmitoylation with licochalcone D reduces NF-κB activity by blocking its nuclear localization and complex formation.

• Why it matters: NF-κB dysregulation is linked to autoimmune diseases, inflammatory disorders, and cancers, making understanding its regulation crucial for developing targeted therapies.
• What they did: The study identified that RelA (p65) is autopalmitoylated at cysteine 197 and 206, which enhances its nuclear localization and activity, and showed that licochalcone D directly inhibits this modification.
• The result: Targeting p65 autopalmitoylation may serve as a therapeutic approach for diseases involving abnormal NF-κB signaling, with licochalcone D as a potential anti-inflammatory agent.