Cullin3/KCTD5 induces monoubiquitination of Delta Np63 alpha 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 Delta Np63 alpha, which is a member of the p53 family. Our further investigation revealed that Cullin3/ KCTD5 can induce monoubiquitination of Delta Np63 alpha. Cullin3/KCTD5 downregulates the DNA-binding affinity of Delta Np63 alpha impairing either its transactivity or its transinhibitory activity. Functionally. Cullin3/KCTD5 abates the proproliferation activity of Delta Np63 alpha. These findings suggest that KCTD5-based CRL3 may mediate monoubiquitination and is a novel regulator of Delta Np63 alpha.