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

Hisashi Koga, Shin Ichi Matsui, Toru Hirota, Shin Ichiro Takebayashi, Katsuzumi Okumura, Hideyuki Saya

Research output: Contribution to journalArticle

49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3799-3809
Number of pages11
JournalOncogene
Volume18
Issue number26
DOIs
Publication statusPublished - 01-07-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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