Interaction of cellular proteins with the leukemia specific fusion proteins DEK-CAN and SET-CAN and their normal counterpart, the nucleoporin CAN

Abstract

The recurrent chromosomal translocation (6;9) is associated with acute myeloid leukemia and results in expression of the DEK-CAN fusion protein. This oncoprotein consists of almost the entire DEK protein fused to the C-terminal two-thirds of the CAN protein. In much the same way, CAN is fused to SET in a patient with acute undifferentiated leukemia, producing a SET-CAN fusion protein. Interestingly, CAN is associated with the nuclear pore complex (NPC) and we recently established its crucial role in nucleocytoplasmic transport processes and cell cycle progression. As a first step in the biochemical analysis of the oncogenic mechanism associated with translocation (6;9), we set out to identify proteins that interact with CAN and its fusion proteins. We found that two proteins specifically co-immunoprecipitate with CAN. One had a molecular mass of 88 kDa protein (CC88) and was determined to associate with the central region of CAN that contains several protein interaction motifs. A second protein of 112 kDa (CC112) was found to interact with the C-terminal nucleoporin-specific repeat of CAN, a region that is supposed to function in nucleocytoplasmic transport. CC112 also interacts with the DEK-CAN and SET-CAN fusion proteins. This finding suggests that CC112 may contribute an essential function to the leukemogenic effect of DEK-CAN and SET-CAN.