Interaction of cellular proteins with the leukemia specific fusion proteins DEK-CAN and SET-CAN and their normal counterpart, the nucleoporin CAN.
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.
Fornerod
M
M
Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Boer
J
J
van Baal
S
S
Morreau
H
H
Grosveld
G
G
D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000473:pathology; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D011233:Precipitin Tests; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C084738:DEK protein, human; D056488:Histone Chaperones; C085914:NUP214 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C513473:SET protein, human; D014157:Transcription Factors