Taken together, our results show that the NB domain is essential to rescue developmental and cancer phenotypes observed upon downregulation of Not3. Since the NB domain is essential for the association of Not3 with the CCR4-NOT complex [27, 28], these data further indicate that the effects observed with downregulation of Not3 are linked to its function within the CCR4-NOT complex. The gene discussed is CNOT3; the disease is cancer.