Protein dimerization between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice
Protein dimerization between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice
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DOI：
10.1002/j.1460-2075.1996.tb00439.x
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发表时间：
1996-03-01
期刊：
影响因子：
11.4
通讯作者：
Rabbitts, TH
中科院分区：
文献类型：
--
作者：
Larson, RC;Lavenir, I;Rabbitts, TH
LMO2 和 TAL1 基因首先通过染色体易位被识别，后来发现编码在正常红细胞发育过程中相互作用的蛋白质。一些T细胞白血病患者存在涉及这两种基因的染色体异常，这意味着LMO2和TAL1在不适当的共表达后协同作用促进肿瘤发生。为了验证这一假设，我们制作了在 T 细胞中共表达 Lmo2 和 Tal1 基因的转基因小鼠。 Lmo2 和 Tal1 蛋白的二聚体在双转基因小鼠而非单转基因小鼠的胸腺细胞中形成。此外，双转基因小鼠的胸腺从出生起就几乎完全充满了未成熟的T细胞，并且这些小鼠比仅具有Lmo2转基因的小鼠早3个月出现T细胞肿瘤。因此，这两种蛋白质之间的相互作用可以改变 T 细胞发育并增强肿瘤发生。这些数据还正式证明 TAL1 是一种癌基因，显然在该系统中充当肿瘤启动子。
The LMO2 and TAL1 genes were first identified via chromosomal translocations and later found to encode proteins that interact during normal erythroid development. Some T cell leukaemia patients have chromosomal abnormalities involving both genes, implying that LMO2 and TAL1 act synergistically to promote tumorigenesis after their inappropriate co-expression. To test this hypothesis, transgenic mice were made which co-express Lmo2 and Tal1 genes in T cells. Dimers of Lmo2 and Tal1 proteins were formed in thymocytes of double but not single transgenic mice. Furthermore, thymuses of double transgenic mice were almost completely populated by immature T cells from birth, and these mice develop T cell tumours similar to 3 months earlier than those with only the Lmo2 transgene. Thus interaction between these two proteins can alter T cell development and potentiate tumorigenesis. The data also provide formal proof that TAL1 is an oncogene, apparently acting as a tumour promoter in this system.