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首页> 外文期刊>Cell cycle >Distinct proliferative and transcriptional effects of the D-type cyclins in vivo.
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Distinct proliferative and transcriptional effects of the D-type cyclins in vivo.

机译：D型细胞周期蛋白在体内具有明显的增殖和转录作用。

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The D-type cyclins (D1, D2 and D3) are components of the cell cycle machinery and govern progression through G(1) phase in response to extracellular signals. Although these proteins are highly homologous and conserved in evolution, they contain distinct structural motifs and are differentially regulated in various cell types. Cyclin D1 appears to play a role in many different types of cancer, whereas cyclins D2 and D3 are less frequently associated with malignancy. In this study, we transiently expressed cyclin D1, D2 or D3 in hepatocytes and analyzed transcriptional networks regulated by each. All three D-type cyclins promoted robust hepatocyte proliferation and marked liver growth, although cyclin D3 stimulated less DNA synthesis than D1 or D2. Accordingly, the three D-type cyclins similarly activated genes associated with cell division. Cyclin D1 regulated transcriptional pathways involved in the metabolism of carbohydrates, lipids, amino acids, and other substrates, whereas cyclin D2 did not regulate these pathways despite having an equivalent effect on proliferation. Comparison of transcriptional profiles following 70% partial hepatectomy and cyclin D1 transduction revealed a highly significant overlap, suggesting that cyclin D1 may regulate diverse cellular processes in the regenerating liver. In summary, these studies provide the first comparative analysis of the transcriptional networks regulated by the D-type cyclins and provide insight into novel functions of these key cell cycle proteins. Further study of the unique targets of cyclin D1 should provide further insight into its prominent role in proliferation, growth and cancer.
机译：D型细胞周期蛋白（D1，D2和D3）是细胞周期机制的组成部分，可响应细胞外信号控制通过G（1）相的进程。尽管这些蛋白质高度同源并在进化中保守，但它们包含不同的结构基序，并在各种细胞类型中受到不同的调控。细胞周期蛋白D1似乎在许多不同类型的癌症中起作用，而细胞周期蛋白D2和D3与恶性肿瘤的相关性较低。在这项研究中，我们在肝细胞中瞬时表达细胞周期蛋白D1，D2或D3，并分析了每个细胞调节的转录网络。尽管细胞周期蛋白D3刺激的DNA合成少于D1或D2，但所有三个D型细胞周期蛋白都促进了强劲的肝细胞增殖和明显的肝生长。因此，三个D型细胞周期蛋白类似地激活与细胞分裂有关的基因。细胞周期蛋白D1调节涉及碳水化合物，脂质，氨基酸和其他底物代谢的转录途径，而细胞周期蛋白D2尽管对增殖具有同等作用，但并未调节这些途径。 70％部分肝切除术后细胞周期蛋白D1和细胞周期蛋白D1转导后的转录谱比较表明，细胞周期蛋白D1可能调节再生肝脏中的多种细胞过程。总之，这些研究为D型细胞周期蛋白调控的转录网络提供了首次比较分析，并深入了解了这些关键细胞周期蛋白的新功能。对细胞周期蛋白D1独特靶标的进一步研究应提供对其在增殖，生长和癌症中的重要作用的进一步了解。

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