Cellular proliferation and transformation induced by HOXB4 and HOXB3 proteins involves cooperation with PBX1
Cellular proliferation and transformation induced by HOXB4 and HOXB3 proteins involves cooperation with PBX1
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DOI：
10.1038/sj.onc.1201883
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发表时间：
1998-07-02
期刊：
影响因子：
8
通讯作者：
Sauvageau, G
中科院分区：
文献类型：
--
作者：
Krosl, J;Baban, S;Sauvageau, G
PBX同源盒基因的产物最初发现于人类白血病的相互易位中，已被证明在体外DNA与HOX蛋白的结合中具有协同作用。尽管越来越多的数据暗示Hox基因在各种癌症的发展中的作用，但对HOX-PBX相互作用在哺乳动物细胞增殖调节和转化诱导中的作用知之甚少。我们建立在现有的Hox诱导的大鼠-1细胞转化模型，以表明Hoxb 4和Hoxb 3诱导的细胞转化和增殖都受到这些细胞中存在的PBX 1水平的极大调节。此外，我们表明，这两个HOX蛋白的转化能力取决于其保守的四肽和同源结构域区域介导的结合PBX和DNA，分别。两者合计，本研究的结果表明，HOX和PBX蛋白之间的合作调节细胞增殖，并强烈表明，合作DIVA结合这两组蛋白质的基础上，Hox诱导的细胞转化。
The products of PBX homeobox genes, which mere initially discovered in reciprocal translocations occurring in human leukemias, have been shown to cooperate in the in vitro DNA binding with HOX proteins. Despite the growing body of data implicating Hox genes in the development of various cancers, little is known about the role of HOX-PBX interactions in the regulation of proliferation and induction of transformation of mammalian cells. We build on the existing model of Hox-induced transformation of Rat-1 cells to show that both cellular transformation and proliferation induced by Hoxb4 and Hoxb3 are greatly modulated by the levels of available PBX1 present in these cells. Furthermore, we show that the transforming capacity of these two HOX proteins depends on their conserved tetrapeptide and homeodomain regions which mediate binding to PBX and DNA, respectively. Taken together, results of this study demonstrate that cooperation between HOX and PBX proteins modulates cellular proliferation and strongly suggest that cooperative DIVA binding by these two groups of proteins represent the basis for Hox-induced cellular transformation.