A human homolog of Drosophila lethal(3)malignant brain tumor (1(3)mbt) protein associates with condensed mitotic chromosomes
A human homolog of Drosophila lethal(3)malignant brain tumor (1(3)mbt) protein associates with condensed mitotic chromosomes
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DOI：
10.1038/sj.onc.1202732
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发表时间：
1999-07-01
期刊：
影响因子：
8
通讯作者：
Saya, H
中科院分区：
文献类型：
--
作者：
Koga, H;Matsui, S;Saya, H
致死（3）恶性脑肿瘤（D-l（3）mbt）基因被认为是果蝇的肿瘤抑制基因之一，其隐性突变与幼虫脑中神经母细胞的恶性转化有关。D-1（3）mbt蛋白与果蝇足中段性梳（Scm）蛋白结构相似，属于多梳组（Polycomb group，PcG）。我们在此分离出D-1（3）mbt基因的第一个人类同源物，命名为h-1（3）mbt。辐射杂交定位和荧光原位杂交（FISH）分析定位h-l（3）mbt基因染色体20 q12。k-l（3）mbt转录本在大多数成人正常组织和培养细胞系中表达。然而，一些癌细胞显著降低h-l（3）mbt蛋白表达。免疫细胞化学研究表明，h-l（3）mbt蛋白呈斑点状散在分布于间期核内，在有丝分裂细胞中与凝聚的染色体完全结合。这种亚细胞定位已被证明是不同的Bmi 1蛋白，这是一个组成部分的PcG复合物。此外，通过使用Cre介导的基因激活系统过量表达h-1（3）mbt蛋白导致正常染色体分离和胞质分裂失败，从而导致U251 MG细胞中多核的形成。这些观察结果表明，h-1（3）mbt蛋白具有不同于PcG蛋白的功能，并可能在细胞分裂的正常进程中发挥作用。
The lethal(3)malignant brain tumor (D-l(3)mbt) gene is considered to be one of the tumor suppressor genes of Drosophila, and its recessive mutations are associated with malignant transformation of the neuroblasts in the larval brain. The structure of D-l(3)mbt protein is similar to Drosophila sex comb on midleg (Scm) protein which is a member of Polycomb group (PcG) proteins. We have isolated here the first human homolog of the D-l(3)mbt gene, designated h-l(3)mbt. Radiation hybrid mapping and fluorescence in situ hybridization (FISH) analysis localized the h-l(3)mbt gene to chromosome 20q12. The k-l(3)mbt transcript is expressed in most of the human adult normal tissues and cultured cell lines. However, some cancer cells markedly reduce the h-l(3)mbt protein expression. Immunocytochemical study revealed that the h-l(3)mbt protein shows a speckled and scattered distribution in interphase nuclei and completely associates with condensed chromosomes in mitotic cells. This subcellular localization has been shown to be different from that of Bmi1 protein which is a component of PcG complex. Furthermore, overexpression of h-l(3)mbt protein by using a Cre-mediated gene activation system leads to failures of proper chromosome segregation and cytokinesis, which result in formation of multinuclei in U251MG cells. These observations suggest that h-l(3)mbt protein has functions distinct from those of PcG proteins and may play a role in proper progression of cell division.