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首页> 外文期刊>Molecular biology of the cell >Growth factor regulation of cyclin D1 mRNA expression through protein synthesis-dependent and -independent mechanisms.
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Growth factor regulation of cyclin D1 mRNA expression through protein synthesis-dependent and -independent mechanisms.

机译：生长因子通过蛋白质合成依赖性和非依赖性机制调节细胞周期蛋白D1 mRNA的表达。

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Overexpression of the cyclin D1/PRAD1 oncogene has been observed in a number of tumorigenic cell lines, suggesting that regulation of D1 expression may represent an important step in the control of cellular proliferation. We have examined the mRNA expression of cyclin D1, as well as two related D-type cyclins, D2 and D3, in response to defined growth factors that control the growth of Balb/c-3T3 fibroblasts. Transcripts for all three D-type cyclins were expressed during the G1 phase of the Balb cell cycle, however only D1 and D3 exhibited periodic induction. Although redundantly expressed, message levels of cyclin D1 and D3 were differentially regulated in regard to kinetics of induction; a modest increase in D3 mRNA was detected near the G1/S boundary, 12 h after serum stimulation of quiescent cells, while abundance of D1 transcript increased 20 to 30-fold, peaking 6 h after addition of serum. Factors such as platelet-derived growth factor (PDGF) that induce competence formation in Balb cells, increased D1 message and protein levels to the same extent as serum but did not affect expression of cyclin D3 and did not stimulate entry into S phase. Progression factors contained within platelet-poor plasma stimulated D1 expression only weakly but acted synergistically with low concentrations of PDGF to increase D1 mRNA to maximum levels. Depletion of protein kinase C severely reduced the ability of PDGF and serum to induce D1 mRNA. PDGF- and serum-mediated elevation of steady-state D1 message levels was in part because of a transcriptional activation of the D1 gene that was independent of protein synthesis. However, protein synthesis was required 3-4 h after serum stimulation for the shut down of D1 transcription leading to the normal decline in message levels after peak induction. Our results indicate that overexpression of cyclin D1 message may result from a disruption of negative regulatory events that repress D1 transcription.
机译：在许多致瘤细胞系中已经观察到细胞周期蛋白D1 / PRAD1癌基因的过表达，这表明D1表达的调节可能代表了控制细胞增殖的重要步骤。我们已经检查了细胞周期蛋白D1以及两个相关的D型细胞周期蛋白D2和D3的mRNA表达，以响应定义的控制Balb / c-3T3成纤维细胞生长的生长因子。在Balb细胞周期的G1期表达了所有三个D型细胞周期蛋白的转录本，但是只有D1和D3表现出周期性的诱导作用。尽管冗余表达，但细胞周期蛋白D1和D3的信息水平在诱导动力学方面有所不同。在血清刺激静止细胞后12 h，在G1 / S边界附近检测到D3 mRNA的适度增加，而D1转录本的丰度增加20至30倍，在添加血清后6 h达到峰值。诸如血小板衍生生长因子（PDGF）等因子可诱导Balb细胞中的能力形成，其D1信息和蛋白质水平增加至与血清相同的程度，但不影响细胞周期蛋白D3的表达且不刺激进入S期。贫血小板血浆中所含的进展因子仅弱地刺激D1表达，但与低浓度的PDGF协同作用以使D1 mRNA增至最大水平。蛋白激酶C的消耗严重降低了PDGF和血清诱导D1 mRNA的能力。 PDGF和血清介导的稳态D1信息水平的升高部分是由于D1基因的转录激活而与蛋白质合成无关。但是，在血清刺激后3-4小时需要蛋白质合成以关闭D1转录，从而导致峰值诱导后消息水平正常下降。我们的结果表明，细胞周期蛋白D1信息的过度表达可能是由于抑制D1转录的负调控事件的破坏所致。

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