fos protooncogene and the regulation of gene expression in adipocyte differentiation.
fos protooncogene and the regulation of gene expression in adipocyte differentiation.
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fos原癌基因和脂肪细胞分化中基因表达的调节。
DOI：
10.1083/jcb.107.3.829
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发表时间：
1988-09
影响因子：
7.8
通讯作者：
Satterberg, B
中科院分区：
文献类型：
--
作者：
Spiegelman, B M;Distel, R J;Ro, H S;Rosen, B S;Satterberg, B
在高等真核生物中，细胞的发育分为几个阶段。该过程的特征通常在于多能性的丧失和可能的细胞命运的限制，导致高度”确定”的细胞，其可以增殖或分化成确定的终末型细胞。细胞分化的过程可以在许多细胞类型中进行研究，其中一些提供了方便的培养系统。我们对脂肪细胞的发育特别感兴趣。在我们的研究中，我们有两个目标。首先，使用脂肪细胞分化作为细胞发育中信号转导过程的模型，由此细胞外刺激导致终产物基因的最终表达、前体细胞特征基因的消失和表型分化。此外，由于脂肪细胞在全身能量平衡的某些病理综合征中起中心作用，最显著的是肥胖、肥胖相关糖尿病和恶病质。（脂肪和肌肉萎缩），我们有兴趣利用基因控制的研究来提高我们对这些疾病的理解。因为癌症是一种涉及细胞生长控制丧失和细胞分化正常模式破坏的疾病，人们对癌基因及其正常细胞对应物（原癌基因）在分化过程中控制基因表达模式的作用非常感兴趣。许多使用导入细胞的癌基因表达的研究已经显示出深远的影响，根据所分析的癌基因和细胞系统，促进或抑制分化（4，5，8，13，17，19，21，24）。这种方法的一个困难是，癌蛋白和基因表达的最终改变之间的联系通常不清楚。我们最近通过不同的方法实现了同样的目标。通过详细研究在脂肪细胞分化过程中参与激活特定基因的顺式和反式作用成分，我们已经确定了第一个与癌基因（fos）相关的基因产物，该基因产物似乎在分化过程中控制基因表达中发挥直接作用。这将是下文讨论的主要问题。
ELLULAR development occurs in several stages in higher eukaryotic organisms. This process is generally characterized by the loss of pluripotency and restriction of possible cell fates, leading to a highly" determined" cell that can either proliferate or differentiate into a defined end-type cell. The process of cell differentiation can be studied in many cell types, some of which offer convenient culture systems. We are particularly interested in the development of fat cells. In our studies we have had two objectives. First, to use adipocyte differentiation as a model for the process of signal transduction in cellular development, whereby extracellular stimulation leads to the ultimate expression of end-product genes, extinction of genes characteristic of the precursor cells, and phenotypic differentiation. In addition, because the adipose cell is centrally involved in certain pathological syndromes of systemic energy balance, most notably obesity, obesity-linked diabetes, and cachexia (fat and muscle wasting), we are interested in using studies of gene control to improve our understanding of these disorders.Because cancer is a disease involving loss of cellular growth control and disruption of the usual pattern of cell differentiation, there has been much interest in the role of oncogenes and their normal cellular counterparts (protooncogenes) in controlling patterns of gene expression during differentiation. Many studies using the expression of oncogenes introduced into cells have shown profound effects, either promoting or inhibiting differentiation depending on the oncogene and cellular system being analyzed (4, 5, 8, 13, 17, 19, 21, 24). One difficulty with this approach has been that the connection between the oncoprotein and the ultimate alterations in gene expression is usually not clear. We have recently approached the same goals through a different method. By studying in detail the cis-and trans-acting components involved in activating a particular gene during adipocyte differentiation, we have identified the first gene product related to an oncogene (fos) which appears to play a direct role in controlling gene expression during differentiation. This will be the major subject discussed below.