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首页> 外文期刊>Molecular and Cellular Biology >Cell cycle regulation of cyclin A gene expression by the cyclic AMP-responsive transcription factors CREB and CREM.
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Cell cycle regulation of cyclin A gene expression by the cyclic AMP-responsive transcription factors CREB and CREM.

机译:循环AMP响应转录因子CREB和CREM对细胞周期蛋白A基因表达的细胞周期调节。

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Cyclin A is a pivotal regulatory protein which, in mammalian cells, is involved in the S phase of the cell cycle. Transcription of the human cyclin A gene is cell cycle regulated. We have investigated the role of the cyclic AMP (cAMP)-dependent signalling pathway in this cell cycle-dependent control. In human diploid fibroblasts (Hs 27), induction of cyclin A gene expression at G1/S is stimulated by 8-bromo-cAMP and suppressed by the protein kinase A inhibitor H89, which was found to delay S phase entry. Transfection experiments showed that the cyclin A promoter is inducible by activation of the adenylyl cyclase signalling pathway. Stimulation is mediated predominantly via a cAMP response element (CRE) located at positions -80 to -73 with respect to the transcription initiation site and is able to bind CRE-binding proteins and CRE modulators. Moreover, activation by phosphorylation of the activators CRE-binding proteins and CRE modulator tau and levels of the inducible cAMP early repressor are cell cycle regulated, which is consistent with the pattern of cyclin A inducibility by cAMP during the cell cycle. These results suggest that the CRE is, at least partly, implicated in stimulation of cyclin A transcription at G1/S.
机译:细胞周期蛋白A是关键的调节蛋白,在哺乳动物细胞中,它参与细胞周期的S期。人细胞周期蛋白A基因的转录受细胞周期调节。我们已经研究了依赖于循环AMP(cAMP)的信号通路在这种依赖细胞周期的控制中的作用。在人类二倍体成纤维细胞(Hs 27)中,G1 / S对细胞周期蛋白A基因表达的诱导被8-bromo-cAMP刺激,并被蛋白激酶A抑制剂H89抑制,发现该蛋白可延迟S期进入。转染实验表明,通过激活腺苷酸环化酶信号通路可以诱导细胞周期蛋白A启动子。刺激主要通过位于相对于转录起始位点-80至-73位置的cAMP应答元件(CRE)介导,并且能够结合CRE结合蛋白和CRE调节剂。而且,通过活化剂CRE结合蛋白和CRE调节剂tau的磷酸化的活化以及可诱导的cAMP早期阻遏物的水平是细胞周期调节的,这与在细胞周期中cAMP诱导的细胞周期蛋白A的模式一致。这些结果表明,CRE至少部分地涉及在G1 / S刺激细胞周期蛋白A转录。

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