AP-1 complex is effector of Hox-induced cellular proliferation and transformation
AP-1 complex is effector of Hox-induced cellular proliferation and transformation
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DOI：
10.1038/sj.onc.1203897
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发表时间：
2000-10-26
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;Sauvageau, G
Hox基因产物，最初被认为是胚胎模式的主要调节因子，也是成人组织正常运作所必需的。也有越来越多的证据表明Hox蛋白与细胞增殖/转化的调节有关。然而，hox相关转化和组织生长的潜在分子机制尚未阐明。利用一个完善的模型系统来研究Hoxb4诱导的细胞增殖变化，我们发现，由于Jun-B和fr -1蛋白水平的显著上调，在Hoxb4转导的细胞中，AP-1活性显著增加。此外，我们还发现，AP-1蛋白表达的特异性变化对于Hoxb4诱导的增殖效应是必要的，这些变化汇聚到cyclin D1水平的增加上，cyclin D1是已知的增殖信号的整合者。因此，我们的观察结果将Hox基因产物与细胞周期机制的关键要素联系起来。
Hox gene products, initially characterized as master regulators of embryonic patterning, are also required for proper functioning of adult tissues. There is also a growing body of evidence that links Hox proteins to regulation of cellular proliferation/transformation. However, the underlying molecular mechanisms of Hox-associated transformation and tissue growth have yet to be elucidated. Using a well established model system for studying changes in cellular proliferation induced by Hoxb4, we show that AP-I activity is markedly increased in Hoxb4-transduced cells due to significant upregulation of Jun-B and Fra-1 protein levels, Furthermore, we also show that the specific changes in AP-1 protein expression are necessary for the proliferation effects induced by Hoxb4, and that these changes converge to increase levels of cyclin D1, a known integrator of proliferation signals. Our observations thus link Hox gene products with key elements of the cell cycle machinery.