The C elegans CBFβ homologue BRO-1 interacts with the Runx factor, RNT-1, to promote stem cell proliferation and self-renewal
The C elegans CBFβ homologue BRO-1 interacts with the Runx factor, RNT-1, to promote stem cell proliferation and self-renewal
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DOI：
10.1242/dev.008276
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发表时间：
2007-11-01
期刊：
影响因子：
4.6
通讯作者：
Woollard, Alison
中科院分区：
文献类型：
--
作者：
Kagoshima, Hiroshi;Nimmo, Rachael;Woollard, Alison
在这份报告中，我们研究了线虫CBFβ同源物bro-1。bro-1突变体具有类似于RNT-1(哺乳动物CBFβ相互作用RUNX因子的线虫同源物)的男性特异性感觉射线丢失表型，这是由于Seam谱系中的细胞分裂失败引起的。我们的研究表明，bro-1和RNT-1形成了促进细胞增殖的复合体，并且bro-1增加了RNT-1与DNA相互作用的亲和力和特异性。与RNT-1一样，bro-1过表达导致Seam细胞数量增加，而bro-1和RNT-1共同过表达导致大量Seam细胞增生。最后，我们发现在某些情况下，bro-1似乎独立于RNT-1发挥作用。这些研究为干细胞中这种重要的癌症相关DNA结合复合体的功能和调控提供了新的见解，并支持了RUNX/CBFβ因子具有致癌潜力的观点。
In this report, we investigate the C. elegans CBF beta homologue, BRO- 1. bro- 1 mutants have a similar male- specific sensory ray loss phenotype to rnt- 1 ( the C. elegans homologue of the mammalian CBF beta- interacting Runx factors), caused by failed cell divisions in the seam lineages. Our studies indicate that BRO- 1 and RNT- 1 form a cell proliferation- promoting complex, and that BRO- 1 increases both the affinity and specificity of RNT- 1- DNA interactions. Overexpression of bro- 1, like rnt- 1, leads to an expansion of seam cell number and co- overexpression of bro- 1 and rnt- 1 results in massive seam cell hyperplasia. Finally, we find that BRO- 1 appears to act independently of RNT- 1 in certain situations. These studies provide new insights into the function and regulation of this important cancer- associated DNA- binding complex in stem cells and support the view that Runx/ CBF beta factors have oncogenic potential.