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首页> 外文期刊>Mechanisms of Development >Drosophila Axud1 is involved in the control of proliferation and displays pro-apoptotic activity
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Drosophila Axud1 is involved in the control of proliferation and displays pro-apoptotic activity

机译：果蝇Axud1参与增殖的控制，并显示促凋亡活性

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摘要

Cell division rates and apoptosis sculpt the growing organs, and its regulation implements the developmental programmes that define organ size and shape. The balance between oncogenes and tumour suppressors modulate the cell cycle and the apoptotic machinery to achieve this goal, promoting and restricting proliferation or, in certain conditions, inducing the apoptotic programme. Analysis of human cancer cells with mutation in AXIN gene has uncovered the potential function of AXUD1 as a tumour suppressor. It has been described that Human AXUD1 is a nuclear protein. We find that a DAxud1-GFP fusion protein is localised to the nucleus during interphase, where it accumulates associated to the nuclear envelope, but becomes distributed in a diffused pattern in the nucleus of mitotic cells. We have analysed the function of the Drosophila AXUD1 homologue, and find that DAxud1 behaves as a tumour suppressor that regulates the proliferation rhythm of imaginal cells. Knocking down the activity of DAxud1 enhances the proliferation of these cells, causing in addition a reduction in cell size. Conversely, the increase in DAxud1 expression impedes cell cycle progression at mitosis through disturbance of Cdk1 activity, and induces the apoptosis of these cells in a JNK-dependent manner.
机译：细胞分裂率和细胞凋亡塑造了成长中的器官，其调节作用执行了定义器官大小和形状的发育程序。癌基因和肿瘤抑制因子之间的平衡调节细胞周期和凋亡机制以实现该目标，从而促进和限制增殖，或在某些条件下诱导凋亡程序。对具有AXIN基因突变的人类癌细胞的分析发现了AXUD1作为肿瘤抑制因子的潜在功能。已经描述了人AXUD1是核蛋白。我们发现，DAxud1-GFP融合蛋白在相间定位于细胞核，在此积累与核被膜相关，但在有丝分裂细胞的细胞核中以分散的模式分布。我们已经分析了果蝇AXUD1同源物的功能，并发现DAxud1充当调节虚拟细胞增殖节律的肿瘤抑制因子。降低DAxud1的活性可增强这些细胞的增殖，从而导致细胞大小的减少。相反，DAxud1表达的增加会通过干扰Cdk1活性而阻止有丝分裂时的细胞周期进程，并以JNK依赖性方式诱导这些细胞的凋亡。

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