Identification of the LMO4 gene encoding an interaction partner of the LIM-binding protein LDB1/NLI1:: a candidate for displacement by LMO proteins in T cell acute leukaemia
Identification of the LMO4 gene encoding an interaction partner of the LIM-binding protein LDB1/NLI1:: a candidate for displacement by LMO proteins in T cell acute leukaemia
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DOI：
10.1038/sj.onc.1202502
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发表时间：
1998-11-26
期刊：
影响因子：
8
通讯作者：
Rabbitts, TH
中科院分区：
文献类型：
--
作者：
Grutz, G;Forster, A;Rabbitts, TH
在儿童T细胞急性白血病中，T细胞癌基因LMO2和LMO2被不同的染色体易位激活。这种疾病的转基因小鼠模型表明，Lmo1和Lmo2的强制表达会导致潜伏期较长的T细胞白血病，而Lmo2的表达会导致T细胞分化程序在显性疾病之前受到抑制。这些功能似乎部分通过LMO1或LMO2与LIM结合蛋白LDB1/NLI1的相互作用而调节。我们现在已经通过与LDB1的相互作用确定了LMO家族的一个新成员，命名为LMO4。LMO4在小鼠的组织中广泛表达，包括成年胸腺(主要是CD4、CDS双阳性T细胞)和胚胎胸腺(主要是CD4、CD8双阴性T细胞)。这些特征表明，LDB1-LMO4的相互作用可能在T细胞发育过程中发挥作用，染色体易位或易位导致的LMO1或LMO2的强制表达可能会取代LMO4，从而在T细胞肿瘤发生之前影响T细胞的分化。
The T cell oncogenes LMO2 and LMO2 are activated by distinct chromosomal translocations in childhood T cell acute leukaemias. Transgenic mouse models of this disease demonstrate that enforced expression of Lmo1 and Lmo2 cause T cell leukaemias with long latency and that Lmo2 expression leads to an inhibition of the T cell differentiation programme, prior to overt disease. These functions appear to be partly mediated by interaction of LMO1 or LMO2 with the LIM-binding protein LDB1/NLI1. We have now identified a new member of the Lmo family, designated Lmo4, via its interaction with Ldb1. Lmo4 is widely expressed in mouse tissues, including adult thymus (mainly CD4, CDS-double positive T cells) and embryonic thymus (mainly CD4, CD8-double negative T cells). These characteristics imply that Ldb1-Lmo4 interaction may function in the T cell developmental programme and that enforced expression of LMO1 or LMO2 by chromosomal translocations or transgenesis may displace Lmo4 from this complex and thereby influence T cell differentiation prior to T cell tumour occurrence.