reported that point mutations commonly found in colorectal and pancreatic carcinomas enhance Smad4 degradation by increasing β-TrCP–mediated Smad4 polyubiquitination.24,25 Our finding that β-TrCP binding to Smad4 is regulated by GSK3 phosphorylations raised the question of whether this increased binding between β-TrCP and Smad4 resulted from an increase in Smad4 GSK3 phosphorylations. This evidence concerns the gene SMAD4 and exocrine pancreatic carcinoma.