STEROID AND GROWTH FACTOR CONTROL OF DIFFERENTIATION

类固醇和生长因子控制分化

• 批准号: 2174541
• 负责人: GORDON M RINGOLD
• 金额: $ 17.18万
• 依托单位: AFFYMAX RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-12-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2174541
• 关键词: adipocytes; binding proteins; biological signal transduction; cell differentiation; fibroblast growth factor; gene expression; genetic mapping; genetic promoter element; genetic recombination; genetic regulatory element; genetic transcription; glucocorticoids; growth factor; growth inhibitors; hormone regulation /control mechanism; immunochemistry; molecular cloning; nucleic acid sequence; platelet derived growth factor; radiotracer; transcription factor; tumor necrosis factor alpha

The ability of specific hormones to influence developmental processes has been amply documented, however, the analysis of underlying mechanisms has been severely compromised by the complexity of the systems being studied and the difficulty in obtaining pure populations of cells that undergo differentiation under controlled conditions. Moreover, those of us interested in vertebrate systems have not had the benefit of genetic approaches to help in dissecting the complex regulatory networks that dictate the timing and implementation of developmental decisions. In somewhat anthropomorphic terms, the central theme of this proposal surrounds the following question. What are the biochemical signals that instruct "determined" cells to not express differentiated functions at inappropriate times and (2) how does the cell sense the environmental cues that instruct it to activate a specified set of tissue-specific genes? It is the nature of this triggering process and the roles that various classes of hormones play in regulating the decision to differentiate that is the focus of our studies. Specifically, we will pursue studies aimed at understanding the mechanisms by which: 1) glucocorticoid hormones accelerate the differentiation of adipogenic cells and 2) certain growth factors (notable FGF and PDGF) prevent differentiation. Major emphasis will be placed on characterizing the regulation and the function of the glucocorticoid-inducible and FGF/PDGF-repressible AP27 gene, the product of which appears to play a key role in triggering the differentiation of TA1 and 3T3-L1 adipocytes. In addition we will attempt to delineate the cis-acting elements and transcription factors that are crucial for regulating the expression of a gene (clone 47/FSP27) that is transcriptionally activated only in differentiated adipocytes. It is among these regulatory factors that we imagine the targets(s) for the hormonal signals ultimately reside. Our goal is to elucidate the pathways that hormonal signals utilize to alter the ability of cells to undergo differentiation. Complex interactions between the growth state of the cell and such hormonal signals will play a prominent role in our studies. We anticipate that the approaches we are taking will help to elucidate fundamental aspects of tissue-specific gene expression, the biochemistry of cell differentiation, and the regulatory networks established by hormonal signal

特定荷尔蒙影响发育过程的能力 已经有充分的文档记录，然而，潜在的分析 机制已经受到了严重损害，因为 正在研究的系统和获得纯种群的困难 在受控条件下进行分化的细胞。 此外，我们这些对脊椎动物系统感兴趣的人还没有 帮助解剖复合体的遗传方法的好处 规定时间安排和实施的监管网络 发展决策。 在有些拟人化的术语中，这项提议的中心主题 围绕着以下问题。什么是生化信号？ 指示“确定的”细胞不表达分化的功能 不适当的时间和(2)细胞如何感知环境 指示它激活指定的一组特定组织的提示 基因?正是这一触发过程的性质和角色 不同类别的荷尔蒙在调节决定方面发挥作用 区分这一点是我们研究的重点。 具体地说，我们会继续进行研究，以了解 其机制是：1)糖皮质激素促进 成脂细胞分化与某些生长因子 (值得注意的是，成纤维细胞生长因子和血小板衍生生长因子)阻止分化。主要重点将是 把重点放在描述规则和功能的特征 糖皮质激素诱导和成纤维细胞生长因子/血小板衍生生长因子抑制的AP27基因，产物 它们似乎在触发分化的过程中起着关键作用 TA1和3T3-L1脂肪细胞。此外，我们还将尝试描述 顺式作用元件和转录因子对 调控一种基因(克隆47/FSP27)的表达 仅在分化的脂肪细胞中转录激活。它是 在这些监管因素中，我们想象中的目标(S) 荷尔蒙信号最终停留在。 我们的目标是阐明荷尔蒙信号利用的途径 改变细胞分化的能力。复合体 细胞的生长状态与这些激素之间的相互作用 信号将在我们的研究中发挥重要作用。我们预料到 我们正在采取的方法将有助于阐明基本方面 组织特异性基因的表达，细胞的生物化学 分化，以及激素信号建立的调控网络

项目成果

Analysis of glucocorticoid unresponsive cell variants using a mouse glucocorticoid receptor complementary DNA clone.

使用小鼠糖皮质激素受体互补 DNA 克隆分析糖皮质激素无反应细胞变体。

• 发表时间: 1986
• 期刊: The Journal of biological chemistry
• 作者: Northrop,JP;Danielsen,M;Ringold,GM
• 通讯作者: Ringold,GM

Glucocorticoid-regulated expression from the 5'-flanking region of the rat alpha 1-acid glycoprotein gene. Requirement for ongoing protein synthesis.

糖皮质激素调节大鼠 α1-酸性糖蛋白基因 5 侧翼区域的表达。

• 发表时间: 1987
• 期刊: The Journal of biological chemistry
• 作者: Klein,ES;Reinke,R;Feigelson,P;Ringold,GM
• 通讯作者: Ringold,GM

Glucocorticoid control of developmentally regulated adipose genes.

糖皮质激素对发育调节脂肪基因的控制。

• DOI: 10.1016/0022-4731(86)90034-8
• 发表时间: 1986
• 期刊: Journal of steroid biochemistry
• 作者: Ringold,GM;Chapman,AB;Knight,DM
• 通讯作者: Knight,DM

Hormone-free mouse glucocorticoid receptors overexpressed in Chinese hamster ovary cells are localized to the nucleus and are associated with both hsp70 and hsp90.

• 发表时间: 1990-11
• 期刊: The Journal of biological chemistry
• 作者: E. R. Sánchez;M. Hirst;L. Scherrer;H. Tang;M. Welsh;J. Harmon;S. Simons;G. Ringold;W. Pratt

A growth factor-repressible gene associated with protein kinase C-mediated inhibition of adipocyte differentiation.

• DOI: 10.1083/jcb.107.1.279
• 发表时间: 1988-07
• 期刊: The Journal of cell biology
• 作者: Navre M;Ringold GM
• 通讯作者: Ringold GM