Koga H, Matsui S, Hirota T, Takebayashi S, Okumura K, Saya H
Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Japan.
Oncogene. 1999 Jul 1;18(26):3799-809. doi: 10.1038/sj.onc.1202732.
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 h-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.
致死性（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-l(3)mbt蛋白的结构与果蝇中腿上的性梳（Scm）蛋白相似，Scm蛋白是多梳蛋白家族（PcG）的成员之一。我们在此分离出了D-l(3)mbt基因的首个人类同源物，命名为h-l(3)mbt。辐射杂种图谱分析和荧光原位杂交（FISH）分析将h-l(3)mbt基因定位于20号染色体q12区域。h-l(3)mbt转录本在大多数人类成人正常组织和培养细胞系中均有表达。然而，一些癌细胞显著降低了h-l(3)mbt蛋白的表达。免疫细胞化学研究表明，h-l(3)mbt蛋白在间期核中呈斑点状和散在分布，在有丝分裂细胞中与浓缩染色体完全结合。这种亚细胞定位已被证明与PcG复合体的组成成分Bmi1蛋白不同。此外，通过使用Cre介导的基因激活系统过表达h-l(3)mbt蛋白会导致U251MG细胞中染色体正确分离和胞质分裂失败，从而形成多核细胞。这些观察结果表明，h-l(3)mbt蛋白具有与PcG蛋白不同的功能，可能在细胞分裂的正常进程中发挥作用。
