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

CAMP在生长控制和分化中的作用--基因调控

• 批准号: 3813353
• 负责人: Y S CHO-CHUNG
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3813353
• 关键词: cell differentiation; cell growth regulation; cyclic AMP; cyclic AMP receptors; enzyme complex; enzyme substrate; gene expression; genetic promoter element; genetic transcription; human tissue; oncogenes; protein kinase A; protein transport; transcription factor

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.

在原核生物中，已知cAMP调节特异性转录。 通过一个明确的机制。cAMP与原核cAMP结合 结合蛋白CRP（cAMP受体蛋白）/CAP（分解代谢物基因激活剂 蛋白质），这种复合物与特定的DNA序列在5 靶基因的末端，调节RNA聚合酶结合靶基因的能力， 的推动者。在哺乳动物细胞中， 荷尔蒙的刺激。刺激物，其作用通过 腺苷酸环化酶和cAMP依赖性蛋白激酶影响 转录效率的几个基因通过结合特异性 不同的顺式作用DNA序列，CRE（cAMP反应因子 元件），位于5非编码区（启动子）。最近，一个地区 含有CRE的蛋白质已经被证明可以结合特定的核蛋白， 各种组织。最近的证据表明，转录调控 cAMP对真核基因的调控需要一种cAMP依赖性蛋白激酶。在 本研究中，我们检测了cAMP依赖性蛋白激酶在基因表达中的作用， 转录。由于cAMP依赖性蛋白激酶仅存在于 在细胞质中，蛋白激酶的任何核功能都必须 伴随着其移位到细胞核。发现RAS 基因抑制、生长抑制、分化（白血病细胞），以及 Ha-MuSV转化NIH/3 T3细胞的表型逆转 cAMP类似物与RII cAMP核转位相关 受体蛋白，蛋白激酶II型的调节亚基， 在模拟处理后10分钟内检测到。因此，核 RII cAMP受体蛋白的易位是一个早期事件， cAMP调节生长和分化。本研究的目的是 提供cAMP共有序列之间相互作用的直接证据 和cAMP受体蛋白（RII）和/或磷蛋白底物 蛋白激酶