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首页> 外文期刊>Cell cycle >Involvement of the specific nucleolar protein SURF6 in regulation of proliferation and ribosome biogenesis in mouse NIH/3T3 fibroblasts
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Involvement of the specific nucleolar protein SURF6 in regulation of proliferation and ribosome biogenesis in mouse NIH/3T3 fibroblasts

机译：特定核仁蛋白冲浪6在小鼠NIH / 3T3成纤维细胞中扩散和核糖体生物的调节中的参与

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摘要

The nucleolar proteins which link cell proliferation to ribosome biogenesis are regarded to be potentially oncogenic. Here, in order to examine the involvement of an evolutionary conserved nucleolar protein SURF6/Rrp14 in proliferation and ribosome biogenesis in mammalian cells, we established stably transfected mouse NIH/3T3 fibroblasts capable of conditional overexpression of the protein. Cell proliferation was monitored in real-time, and various cell cycle parameters were quantified based on flow cytometry, Br-dU-labeling and conventional microscopy data. We show that overexpression of SURF6 accelerates cell proliferation and promotes transition through all cell cycle phases. The most prominent SURF6 pro-proliferative effects include a significant reduction of the population doubling time, from 19.8 +/- 0.7 to 16.2 +/- 0.5hours (t-test, p < 0.001), and of the length of cell division cycle, from 17.6 +/- 0.6 to 14.0 +/- 0.4hours (t-test, p < 0.001). The later was due to the shortening of all cell cycle phases but the length of G1 period was reduced most, from 5.7 +/- 0.4 to 3.8 +/- 0.3hours, or by approximate to 30%, (t-test, p < 0.05). By Northern blots and qRT-PCR, we further showed that the acceleration of cell proliferation was concomitant with an accumulation of rRNA species along both ribosomal subunit maturation pathways. It is evident, therefore, that like the yeast homologue Rrp14, mammalian SURF6 is involved in various steps of rRNA processing during ribosome biogenesis. We concluded that SURF6 is a novel positive regulator of proliferation and G1/S transition in mammals, implicating that SURF6 is a potential oncogenic protein, which can be further studied as a putative target in anti-cancer therapy.
机译：将细胞增殖与核糖体生物发生的核仁蛋白被认为是可能致癌的。这里，为了检查哺乳动物细胞增殖和核糖体生物发生的进化保守的核仁蛋白冲浪6 / RRP14的累积，我们建立了能够有条件过表达蛋白质的稳定转染的小鼠NIH / 3T3成纤维细胞。实时监测细胞增殖，基于流式细胞术，BR-DU标记和传统显微镜数据量化各种细胞周期参数。我们表明Surf6的过度表达加速细胞增殖并通过所有细胞周期阶段促进过渡。最突出的冲浪6促增强效果包括从19.8 +/- 0.7至16.2 +/- 0.7至16.2 +/- 0.7至0.5hours（t检验，p <0.001）和细胞分裂周期长度的大幅减少，从17.6 +/- 0.6至14.0 +/- 0.4小时（T检验，P <0.001）。后来是由于缩短了所有细胞周期阶段，但G1周期的长度大部分减少，从5.7 +/- 0.4到3.8 +/- 0.3hours，或近似为30％，（t检验，p < 0.05）。通过Northern印迹和QRT-PCR，我们进一步表明，细胞增殖的加速度伴随着核糖体亚基成熟途径的RRNA物种的积累。因此，很明显，就像酵母同源物RRP14一样，哺乳动物冲浪6在核糖体生物发生期间参与rRNA加工的各种步骤。我们得出结论，Surf6是哺乳动物的新型阳性调节剂和哺乳动物的G1 / s过渡，含有Surf6是潜在的致癌蛋白质，可以进一步研究抗癌治疗的推定靶标。

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