mel-18, a Polycomb group-related mammalian gene, encodes a transcriptional negative regulator with tumor suppressive activity.
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.
Division of Molecular Immunology, School of Medicine, Chiba University, Japan.
M
M
Kanno
M
M
Hasegawa
A
A
Ishida
K
K
Isono
M
M
Taniguchi
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011506:Proteins / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019105:Random Amplified Polymorphic DNA Technique; D012097:Repressor Proteins; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection
C489421:Bmi1 protein, mouse; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; C489348:PCGF2 protein, human; C066770:Pc protein, Drosophila; C066476:Pcgf6 protein, mouse; D011506:Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D004247:DNA; D063150:Polycomb Repressive Complex 1