The human formin-binding protein 17 (FBP17) interacts with sorting nexin, SNX2, and is an MLL-fusion partner in acute myelogeneous leukemia
The human formin-binding protein 17 (FBP17) interacts with sorting nexin, SNX2, and is an MLL-fusion partner in acute myelogeneous leukemia
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DOI：
10.1073/pnas.121433898
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发表时间：
2001-07-17
影响因子：
11.1
通讯作者：
Borkhardt, A
中科院分区：
文献类型：
--
作者：
Fuchs, U;Rehkamp, G;Borkhardt, A
我们在 11q23 克隆了 MLL 基因的融合伴侣，并将其鉴定为编码人福尔马林结合蛋白 17（FBP17）的基因。它将染色体 9q34 着丝粒映射到 ABL。基因融合是由复杂的染色体重排产生的，该重排通过荧光原位杂交与 9 号和 11 号染色体上的各种探针作为 ins(11;9)(q23;q34)inv(11)(q13q23) 来解决。重排产生 5'-MLL/FBP17-3' 融合 mRNA。我们用 MLL/FBP17 逆转录病毒转导小鼠骨髓祖细胞，以测试其转化能力。与 MLL/ENL、MLL/ELL 和其他 MLL 融合基因相比，MLL/FBP17 在连续重铺实验中没有给出阳性读数。因此，我们假设可能需要额外的协同遗传异常才能建立完整的恶性表型。 FBP17 由 C 端 Src 同源 3 结构域和 N 端区域组成，该区域与细胞分裂周期蛋白 cdc15（裂殖酵母中肌动蛋白细胞骨架的调节因子）同源。两个结构域均由共有的 Rho 结合基序分隔，该基序已在不同的 Rho 相互作用伙伴（例如 Rhotekin 和 Rhophilin）中发现。我们通过酵母双杂交测定评估了 FBP17 和 Rho 家族成员是否在体内相互作用。然而，所测试的各种 Rho 蛋白均未与 FBP17 相互作用。我们筛选了人类肾脏文库，并鉴定了一种分选连接蛋白 SNX2，作为 FBP17 的蛋白质相互作用伴侣。这些数据提供了表皮生长因子受体途径和 MLL 融合蛋白之间的联系。
We have cloned a fusion partner of the MLL gene at 11q23 and identified it as the gene encoding the human formin-binding protein 17, FBP17. It maps to chromosome 9q34 centromeric to ABL. The gene fusion results from a complex chromosome rearrangement that was resolved by fluorescence in situ hybridization with various probes on chromosomes 9 and 11 as an ins(11;9)(q23;q34)inv(11)(q13q23). The rearrangement resulted in a 5 ' -MLL/FBP17-3 ' fusion mRNA. We retrovirally transduced murine-myeloid progenitor cells with MLL/FBP17 to test its transforming ability. In contrast to MLL/ENL, MLL/ELL and other MLL-fusion genes, MLL/FBP17 did not give a positive readout in a serial replating assay. Therefore, we assume that additional cooperating genetic abnormalities might be needed to establish a full malignant phenotype. FBP17 consists of a C-terminal Src homology 3 domain and an N-terminal region that is homologous to the cell division cycle protein, cdc15, a regulator of the actin cytoskeleton in Schizosaccharomyces pombe. Both domains are separated by a consensus Rho-binding motif that has been identified in different Rho-interaction partners such as Rhotekin and Rhophilin. We evaluated whether FBP17 and members of the Rho family interact in vivo with a yeast two-hybrid assay. None of the various Rho proteins tested, however, interacted with FBP17. We screened a human kidney library and identified a sorting nexin, SNX2, as a protein interaction partner of FBP17. These data provide a link between the epidermal growth factor receptor pathway and an MLL fusion protein.