mel-18, a Polycomb group-related mammalian gene, encodes a transcriptional negative regulator with tumor suppressive activity

EMBO J. 1995 Nov 15;14(22):5672-8. doi: 10.1002/j.1460-2075.1995.tb00254.x.

Abstract

The mammalian mel-18/bmi-1 gene products share an amino acid sequence and a secondary structure, including a RING-finger motif, with the Drosophila Polycomb group (PcG) gene products Psc and Su(z)2, implying that they represent a gene family with related functions. As Drosophila PcG gene products are thought to function as transcriptional repressors by modifying chromatin structure, Mel-18/Bmi-1 might be expected to have similar activities. Here we have analyzed the function of mel-18 and found that Mel-18 acts as a transcriptional repressor via its target DNA sequence, 5'-GACTNGACT-3'. Interestingly, this binding sequence is found within regulatory or non-coding regions of various genes, including the c-myc, bcl-2 and Hox genes, suggesting diverse functions of mel-18 as the mammalian homolog of the PcG gene. We also demonstrate that mel-18 has tumor suppressor activity, in contrast to bmi-1, which has been defined as a proto-oncogene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • Binding Sites
  • DNA / metabolism
  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins*
  • Gene Expression Regulation*
  • Genes, Tumor Suppressor*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Sequence Data
  • Neoplasms, Experimental / genetics
  • Nuclear Proteins / genetics
  • Oligodeoxyribonucleotides
  • Oligonucleotides, Antisense / metabolism
  • Polycomb Repressive Complex 1
  • Proteins / genetics*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics
  • Random Amplified Polymorphic DNA Technique
  • Repressor Proteins*
  • Sequence Homology, Nucleic Acid
  • Transcription, Genetic
  • Transfection

Substances

  • Bmi1 protein, mouse
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Drosophila Proteins
  • MAS1 protein, human
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • Oligonucleotides, Antisense
  • PCGF2 protein, human
  • Pc protein, Drosophila
  • Pcgf6 protein, mouse
  • Proteins
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • DNA
  • Polycomb Repressive Complex 1