CDK4 and familial pancreatic carcinoma: Distinct from Smurf1-mediated proteolytic degradation of RUNX2, it has been demonstrated that cyclin D1/Cdk4 complex phosphorylates RUNX2 and promotes its degradation in an ubiquitin/proteasome-dependent manner.52 In addition, several lines of evidence suggest that Smurf1 has a pro-oncogenic potential.53, 54 In a good agreement with this notion, Shain et al.55 described that Smurf1 gene is amplified in certain subset of human pancreatic cancers and might contribute to their invasiveness.