Transcriptional cross-regulation of RUNX1 by RUNX3 in human B cells
Transcriptional cross-regulation of RUNX1 by RUNX3 in human B cells
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DOI：
10.1038/sj.onc.1208404
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发表时间：
2005-03-10
期刊：
影响因子：
8
通讯作者：
Farrell, PJ
中科院分区：
文献类型：
--
作者：
Spender, LC;Whiteman, HJ;Farrell, PJ
RUNX转录因子在发育和许多类型的人类癌症中都很重要。它们可以作为转录激活因子或抑制因子，也可以是原癌基因或肿瘤抑制因子。了解它们的调节和相互作用可以解释RUNX因子如何促进这些不同的、经常相反的生物过程。我们发现RUNX3调控RUNX1的表达，导致RUNX3和RUNX1在人B淋巴样细胞系中互斥表达。RUNX3通过特异性结合启动子转录起始处附近的保守RUNX位点来抑制RUNX1 P1启动子。淋巴母细胞样细胞中siRNA抑制RUNX3导致RUNX1表达增加，表明RUNX3生理水平的持续表达需要维持抑制。此外，RUNX3的表达是eb病毒永生化B细胞高效增殖所必需的。因此，不同RUNX家族成员之间的交叉调控是控制RUNX蛋白表达的一种手段，现在在解释由于RUNX3肿瘤抑制功能丧失或基因复制或易位事件引起的病理变化时必须考虑。
RUNX transcription factors are important in development and in numerous types of human cancer. They act as either transcriptional activators or repressors and can be proto-oncogenes or tumour suppressors. Understanding their regulation and interaction may explain how RUNX factors contribute to such different and often opposing biological processes. We show that RUNX3 regulates RUNX1 expression, contributing to the mutually exclusive expression of RUNX3 and RUNX1 in human B lymphoid cell lines. RUNX3 repressed the RUNX1 P1 promoter by binding specifically to conserved RUNX sites near the transcription start of the promoter. siRNA inhibition of RUNX3 in lymphoblastoid cells resulted in increased RUNX1 expression, indicating that continuous expression of physiological levels of RUNX3 is required to maintain repression. Furthermore, expression of RUNX3 was required for efficient proliferation of B cells immortalized by Epstein-Barr virus. Cross-regulation between different RUNX family members is therefore a means of controlling RUNX protein expression and must now be considered in the interpretation of pathological changes due to loss of RUNX3 tumour suppressor function or following gene duplication or translocation events.