ROLE OF CAMP IN GROWTH CONTROL AND DIFFERENTIATION--GENE REGULATION

在原核生物中，cAMP被认为调节特定的转录。 基因通过一种明确的机制。CAMP与原核细胞cAMP结合 结合蛋白CRP(cAMP受体蛋白)/CAP(分解代谢基因激活剂 蛋白质)，该复合体与第5位的特定DNA序列相互作用 靶基因末端，调节RNA聚合酶结合的能力 推动者。在哺乳动物细胞中，基因表达会因此而改变 荷尔蒙的刺激。刺激物，其作用是通过 腺苷环化酶和cAMP依赖的蛋白激酶影响 几种基因通过结合特定基因的转录效率 识别顺式作用DNA序列的因素，Cre(cAMP反应 元件)，位于5个非编码(启动子)区域。最近，一个地区 含有Cre的核蛋白已被证明能结合特定的核蛋白 各种纸巾。最近的证据表明，转录调控 CAMP对真核基因的调控需要cAMP依赖的蛋白激酶。在……里面 本研究中，我们研究了cAMP依赖的蛋白激酶在基因中的作用 抄写。因为cAMP依赖蛋白激酶是唯一存在 在细胞质中，蛋白激酶的任何核功能必须是 伴随着它移位到细胞核。结果发现，RAS 基因抑制、生长抑制、分化(白血病细胞)和 定点选择性逆转Ha-MuSV转化的NIH/3T3细胞表型 CAMP类似物与RII cAMP核转位相关 受体蛋白，蛋白激酶II型的调节亚单位，它 在模拟处理后10分钟内检测到。因此，核能 RII cAMP受体蛋白易位是一种早期事件 CAMP对生长分化的调节作用。这项研究的目标是 提供cAMP共识序列之间相互作用的直接证据 和cAMP受体蛋白(RII)和/或 蛋白激酶。

In prokaryotes, cAMP is known to regulate the transcription of specific genes by a well-defined mechanism. cAMP binds to the prokaryotic cAMP binding protein CRP (cAMP receptor protein)/CAP (catabolite gene activator protein), and this complex interacts with specific DNA sequences at the 5 ends of targeted genes, modulating the ability of RNA polymerase to bind to the promoters. In mammalian cells, gene expression is altered in response to stimulation by hormones. Stimuli whose action is mediated through adenylate cyclase and cAMP-dependent protein kinase influence the transcriptional efficiency of several genes through the binding of specific factors to distinct cis-acting DNA sequences, CRE (cAMP responsive element), located in the 5 noncoding (promoter) region. Recently, a region containing the CRE has been shown to bind specific nuclear proteins from various tissues. Recent evidence suggests that transcriptional regulation of eukaryotic genes by cAMP requires a cAMP-dependent protein kinase. In this study, we examined the role of cAMP-dependent protein kinase in gene transcription. Since cAMP-dependent protein kinase is exclusively present in the cytoplasm, any nuclear function of the protein kinase must be accompanied by its translocation to the nucleus. It was found that the ras gene suppression, growth inhibition, differentiation (leukemic cells), and phenotypic reversion of Ha-MuSV-transformed NIH/3T3 cells by site-selective cAMP analogs correlated with the nuclear translocation of the RII cAMP receptor protein, the regulatory subunit of protein kinase type II, which was detected within 10 min after the analog treatment. Thus, the nuclear translocation of the RII cAMP receptor protein is an early event in the cAMP regulation of growth and differentiation. The goal of this study is to provide direct evidence of interaction between the cAMP consensus sequences and cAMP receptor protein (RII) and/or a phosphoprotein substrate of protein kinase.