Cullin3/KCTD5 induces monoubiquitination of ΔNp63α and impairs its activity.

Potassium channel tetramerization domain containing 5 (KCTD5) was previously documented as a component of the Cullin3-RING ligase (CRL3). It has been reported that KCTD5 can induce enrichment of polyubiquitinated proteins, and KCTD5-based CRL3 destabilizes several proteins. In our present study, we report that KCTD5 may physically interact with ΔNp63α, which is a member of the p53 family. Our further investigation revealed that Cullin3/KCTD5 can induce monoubiquitination of ΔNp63α. Cullin3/KCTD5 downregulates the DNA-binding affinity of ΔNp63α, impairing either its transactivity or its transinhibitory activity. Functionally, Cullin3/KCTD5 abates the proproliferation activity of ΔNp63α. These findings suggest that KCTD5-based CRL3 may mediate monoubiquitination and is a novel regulator of ΔNp63α.