PMID- 10445843 OWN - NLM STAT- MEDLINE DCOM- 19990907 LR - 20201209 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 18 IP - 26 DP - 1999 Jul 1 TI - A human homolog of Drosophila lethal(3)malignant brain tumor (l(3)mbt) protein associates with condensed mitotic chromosomes. PG - 3799-809 AB - 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. FAU - Koga, H AU - Koga H AD - Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Japan. FAU - Matsui, S AU - Matsui S FAU - Hirota, T AU - Hirota T FAU - Takebayashi, S AU - Takebayashi S FAU - Okumura, K AU - Okumura K FAU - Saya, H AU - Saya H LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (Chromosomal Proteins, Non-Histone) RN - 0 (L3MBTL1 protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Repressor Proteins) RN - 0 (Tumor Suppressor Proteins) SB - IM MH - Adult MH - Amino Acid Sequence MH - Animals MH - Brain Neoplasms/genetics/pathology MH - Cell Division/drug effects MH - Cell Line MH - Chromosomal Proteins, Non-Histone MH - Chromosomes, Human/*metabolism MH - Chromosomes, Human, Pair 20/*genetics MH - Drosophila melanogaster/*genetics MH - Expressed Sequence Tags MH - Gene Expression Regulation MH - Genes, Recessive MH - *Genes, Tumor Suppressor MH - Glioma/genetics/pathology MH - Humans MH - In Situ Hybridization, Fluorescence MH - Interphase MH - *Mitosis MH - Molecular Sequence Data MH - Neoplasm Proteins/deficiency/genetics/*metabolism MH - Polymerase Chain Reaction MH - Rats MH - Repressor Proteins MH - Sequence Alignment MH - Sequence Homology, Amino Acid MH - Species Specificity MH - Subcellular Fractions MH - Transcriptional Activation MH - Tumor Cells, Cultured MH - Tumor Suppressor Proteins EDAT- 1999/08/13 00:00 MHDA- 1999/08/13 00:01 CRDT- 1999/08/13 00:00 PHST- 1999/08/13 00:00 [pubmed] PHST- 1999/08/13 00:01 [medline] PHST- 1999/08/13 00:00 [entrez] AID - 10.1038/sj.onc.1202732 [doi] PST - ppublish SO - Oncogene. 1999 Jul 1;18(26):3799-809. doi: 10.1038/sj.onc.1202732.