Fornerod M, Boer J, van Baal S, Morreau H, Grosveld G
Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Oncogene. 1996 Oct 17;13(8):1801-8.
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.
复发性染色体易位（6；9）与急性髓系白血病相关，并导致DEK-CAN融合蛋白的表达。这种癌蛋白几乎由整个DEK蛋白与CAN蛋白的C端三分之二融合而成。同样，在一名急性未分化白血病患者中，CAN与SET融合，产生SET-CAN融合蛋白。有趣的是，CAN与核孔复合体（NPC）相关，我们最近确定了它在核质运输过程和细胞周期进程中的关键作用。作为对与易位（6；9）相关的致癌机制进行生化分析的第一步，我们着手鉴定与CAN及其融合蛋白相互作用的蛋白质。我们发现有两种蛋白质能与CAN特异性地共免疫沉淀。一种是分子量为88 kDa的蛋白质（CC88），它被确定与CAN的中央区域相关，该区域包含几个蛋白质相互作用基序。另一种112 kDa的蛋白质（CC112）被发现与CAN的C端核孔蛋白特异性重复序列相互作用，该区域被认为在核质运输中发挥作用。CC112也与DEK-CAN和SET-CAN融合蛋白相互作用。这一发现表明，CC112可能对DEK-CAN和SET-CAN的致白血病作用发挥重要功能。
