A human homolog of Drosophila lethal(3)malignant brain tumor (1(3)mbt) protein associates with condensed mitotic chromosomes

Department of Tumor Genetics and Biology, Kumamoto University, Kumamoto, Kumamoto, Japan
Oncogene (Impact Factor: 8.56). 08/1999; 18(26):3799-809. DOI: 10.1038/sj.onc.1202732
Source: PubMed

ABSTRACT 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.

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Available from: Hideyuki Saya, May 02, 2014
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    • "Interestingly, heterozygous mutants of other PRC1 genes (Pc, Psc, Asx) also display chromatid segregation defects, whereas impaired chromatin condensation and misalignment of chromosomes at the metaphase plate have been observed in E(z) mutants (O'Dor et al., 2006). In contrast to other PRC1 proteins, human L3MBTL1 associates with condensed mitotic chromosomes, and its overexpression leads to chromosome segregation defects, failure in cytokinesis, and the formation of multinucleated cells (Koga et al., 1999). PRSET7 also remains associated with chromosomes during mitosis and appears to be required for chromosome condensation (Oda et al., 2009; Rice et al., 2002). "
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    • "The protein functions as a transcriptional repressor and is requisite for mitotic progression (Boccuni et al., 2003). Overexpression of L3MBTL1 leads to improper chromosome segregation and cytokinesis, thereby inducing multinucleated cell formation (Koga et al., 1999). In a candidate screen for effector proteins, the MBT region of L3MBTL1 was found to bind methylated lysine residues in the context of histone tails (Kim et al., 2006). "
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    • "Although it is predicted that the mbt domain might possess a strong transcription-repressing activity (Boccuni et al, 2003), the physiological function(s) of the mbt-containing PcG proteins are yet unclear. Interestingly , the human homolog of the l(3)mbt gene (H-L(3)MBT gene) maps to chromosome 20q12, within a common deleted region associated with myeloid hematopoietic malignancies (Koga et al, 1999; Bench et al, 2000; MacGrogan et al, 2001; Li et al, 2004). This may also suggest a possible linkage of the mbt-containing PcG proteins and hematopoiesis. "
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