MEL-18, A POLYCOMB GROUP-RELATED MAMMALIAN GENE, ENCODES A TRANSCRIPTIONAL NEGATIVE REGULATOR WITH TUMOR SUPPRESSIVE ACTIVITY
MEL-18, A POLYCOMB GROUP-RELATED MAMMALIAN GENE, ENCODES A TRANSCRIPTIONAL NEGATIVE REGULATOR WITH TUMOR SUPPRESSIVE ACTIVITY
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DOI：
10.1002/j.1460-2075.1995.tb00254.x
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发表时间：
1995-11-15
期刊：
影响因子：
11.4
通讯作者：
TANIGUCHI, M
中科院分区：
文献类型：
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作者：
KANNO, M;HASEGAWA, M;TANIGUCHI, M
哺乳动物的Mel-18/Bmi-1基因产物与果蝇PcG基因产物PSC和SU(Z)2具有相同的氨基酸序列和包括环指基序的二级结构，这意味着它们代表了一个具有相关功能的基因家族。由于果蝇PcG基因产物被认为是通过改变染色质结构而起转录抑制作用的，Mel-18/Bmi-1可能具有类似的活性。我们分析了Mel-18的功能，发现Mel-18通过其靶DNA序列5‘-GACTNGACT-3’发挥转录抑制作用该结合序列位于多种基因的调控或非编码区，包括c-myc、bcl2和Hox基因，提示Mel-18作为PcG基因的哺乳动物同源物具有不同的功能。我们还证明了Mel-18具有肿瘤抑制活性，而Bmi-1被定义为原癌基因。
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 protooncogene.