BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells
BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells
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DOI：
10.1038/ni1245
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发表时间：
2005-10-01
影响因子：
30.5
通讯作者：
Dalla-Favera, R
中科院分区：
文献类型：
--
作者：
Phan, RT;Saito, M;Dalla-Favera, R
BCL 6原癌基因编码一个转录抑制因子，是生发中心形成所必需的，并与淋巴瘤发生有关。BCL 6通过直接结合特定的DNA序列并抑制靶基因的转录来发挥作用。在这里，我们报告了一种替代机制，BCL 6控制转录的基因缺乏BCL 6结合位点，并表明这种机制是需要预防肿瘤抑制p53非依赖性细胞周期停滞在生发中心B细胞。BCL 6与转录激活因子Miz-1相互作用，并通过Miz-1与启动子结合，抑制细胞周期阻滞基因CDKN 1A的转录。通过这种机制，BCL 6可以在正常免疫应答期间促进生发中心的增殖性扩张，并且当失调时，促进B细胞淋巴瘤的病理性扩张。
The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center formation and has been linked to lymphomagenesis. BCL6 functions by directly binding to specific DNA sequences and suppressing the transcription of target genes. Here we report an alternative mechanism by which BCL6 controls the transcription of genes lacking a BCL6 binding site and show that this mechanism was required for the prevention of tumor suppressor p53 - independent cell cycle arrest in germinal center B cells. BCL6 interacted with the transcriptional activator Miz-1 and, via Miz-1, bound to the promoter and suppressed transcription of the cell cycle arrest gene CDKN1A. Through this mechanism, BCL6 may facilitate the proliferative expansion of germinal centers during the normal immune response and, when deregulated, the pathological expansion of B cell lymphomas.