CKIP-1 couples Smurf1 ubiquitin ligase with Rpt6 subunit of proteasome to promote substrate degradation.

CKIP-1 is an activator of the Smurf1 ubiquitin ligase acting to promote the ubiquitylation of Smad5 and MEKK2. The mechanisms involved in the recognition and degradation of these substrates by the proteasome remain unclear. Here, we show that CKIP-1, through its leucine zipper, interacts directly with the Rpt6 ATPase of the 19S regulatory particle of the proteasome. CKIP-1 mediates the Smurf1-Rpt6 interaction and delivers the ubiquitylated substrates to the proteasome. Depletion of CKIP-1 reduces the degradation of Smurf1 and its substrates by Rpt6. These findings reveal an unexpected adaptor role of CKIP-1 in coupling the ubiquitin ligase and the proteasome.