In this study by the Zhang group, they found that PDK1 is a novel substrate of SMURF1, and the resultant poly-neddylated chain of PDK1 at K163 residue serves as a recognition signal for binding to SETDB1 (SET domain bifurcated histone lysine methyltransferase 1), an oncoprotein overexpressed in many human cancers (Lazaro-Camp et al., 2021), via the N-terminal NEDD8-binding domain of SETDB1. Here, PDK1 is linked to cancer.