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. 1995 Nov 15;14(22):5672–5678. doi: 10.1002/j.1460-2075.1995.tb00254.x

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

M Kanno 1, M Hasegawa 1, A Ishida 1, K Isono 1, M Taniguchi 1
PMCID: PMC394682  PMID: 8521824

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.

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