We also provide mechanistic evidence that CNOT3 is genetically linked to APC through CtBP1. Taken together with our findings that CNOT3 mutations are present in approximately 20% of FAP adenomas, we conclude that proper CNOT3 function is important for intestinal development and that CNOT3 inactivation might work in concert with APC deficiency to prevent intestinal differentiation and potentially advance colon adenomas to a more transformed state. Here, APC is linked to Familial adenomatous polyposis.