THE RHOMBOTIN FAMILY OF CYSTEINE-RICH LIM-DOMAIN ONCOGENES - DISTINCT MEMBERS ARE INVOLVED IN T-CELL TRANSLOCATIONS TO HUMAN CHROMOSOME-11P15 AND CHROMOSOME-11P13
THE RHOMBOTIN FAMILY OF CYSTEINE-RICH LIM-DOMAIN ONCOGENES - DISTINCT MEMBERS ARE INVOLVED IN T-CELL TRANSLOCATIONS TO HUMAN CHROMOSOME-11P15 AND CHROMOSOME-11P13
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DOI：
10.1073/pnas.88.10.4367
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发表时间：
1991-05-01
影响因子：
11.1
通讯作者：
RABBITTS, TH
中科院分区：
文献类型：
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作者：
BOEHM, T;FORONI, L;RABBITTS, TH
T细胞白血病的染色体易位涉及人类11号染色体11p15带的短臂，破坏了Rhombotin基因。该基因编码一种带有重复的半胱氨酸富集区的蛋白质，称为LIM结构域，与锌结合蛋白和铁氧还蛋白的铁硫中心同源。Rhombotin基因的两个同源基因现在已经被分离出来。其中一个被命名为RHOM-2，位于人类染色体11号带11p13上，发生了一系列T细胞白血病特异性易位；11p13上的所有易位断裂点都位于RHOM-2基因的上游。人和小鼠的RHOM-2高度保守，和Rombotin一样，编码两个串联的富含半胱氨酸的LIM结构域。RHOM-2mRNA在小鼠发育早期的中枢神经系统、肺、肾、肝、脾等组织中均有表达，但在胸腺中的表达水平很低。另一个基因，命名为RHOM-3，不在11号染色体上，但也与Rombotin的LIM结构域保持同源性。由于RHOM-2基因是T细胞肿瘤中常见的染色体损伤部位，因此进一步检查了rombotin基因附近易位的一致性。发现了与Rhombotin相邻的第二个易位，其位置与上一个例子中的相同。因此，染色体11p15(Rhombotin)和11p13(RHOM-2)是T细胞白血病中一致的染色体易位部位，而11p15靶点较少涉及。这些结果将Rhombotin基因家族定义为一类具有重复的富含半胱氨酸的LIM结构域的T细胞癌基因。
A chromosomal translocation in a T-cell leukemia involving the short arm of human chromosome 11 at band 11p15 disrupts the rhombotin gene. This gene encodes a protein with duplicated cysteine-rich regions called LIM domains, which show homology to zinc-binding proteins and to iron-sulfur centers of ferredoxins. Two homologues of the rhombotin gene have now been isolated. One of these, designated Rhom-2, is located on human chromosome 11 at band 11p13, where a cluster of T-cell leukemia-specific translocations occur; all translocation breakpoints at 11p13 are upstream of the Rhom-2 gene. Human and mouse Rhom-2 are highly conserved and, like rhombotin, encode two tandem cysteine-rich LIM domains. Rhom-2 mRNA is expressed in early mouse development in central nervous system, lung, kidney, liver, and spleen but only very low levels occur in thymus. The other gene, designated Rhom-3, is not on chromosome 11 but also retains homology to the LIM domain of rhombotin. Since the Rhom-2 gene is such a common site of chromosomal damage in T-cell tumors, the consistency of translocations near the rhombotin gene was further examined. A second translocation adjacent to rhombotin was found and at the same position as in the previous example. Therefore, chromosome bands 11p15 (rhombotin) and 11p13 (Rhom-2) are consistent sites of chromosome translocation in T-cell leukemia, with the 11p15 target more rarely involved. The results define the rhombotin gene family as a class of T-cell oncogenes with duplicated cysteine-rich LIM domains.