Regulation and Function of the Erythroid Transcription Factor NF-E2
红系转录因子 NF-E2 的调节和功能
基本信息
- 批准号:9506327
- 负责人:
- 金额:$ 28.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:1995
- 资助国家:美国
- 起止时间:1995-09-01 至 1998-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
9506327 Pilz The transcription factor NF-E2 (a complex of two proteins, p45 and p18) binds to specific DNA sequences in the regulatory regions of erythroid genes and appears to be necessary for the transcriptional activation of these genes during red blood cell maturation. The PI has recently found that murine erythroleukemia cells (MEL), a model system of red blood cells, that are deficient in cAMP dependent protein kinase (A kinase), an enzyme involved in signal transduction, are severely impaired in their ability to mature and activate erythroid genes. The also have abnormal binding of NF-E2. Preliminary experiments suggested that A-kinase regulates NF-E2 by phosphorylating p45 and by regulating the complex formation of p45 and p18. The experiments in this grant will test examine this further. The phosphorylation of p45 by A kinase will be studied by determining which amino acids are phosphorylated, to see if this phosphorylation occurs during red blood cell maturation, and determibne if this phosphorylation of p45 changes its its complex formation with p18 and alters the ability of NF-E2 to activate erythroid genes. The next series of experiments will examine proteins which interact with NF-E2 and see if these interactions alter its function. %%% The results of this research will increase our knowledge of the regulation of NF-E2 function and define the role of A- kinase during red blood cell maturation. They will also provide information on the general functions of this enzyme in signal transduction. ***
9506327 PILZ转录因子核因子-E2(P45和P18两种蛋白质的复合体)与红系基因调节区的特定DNA序列结合,似乎是红血球成熟期间这些基因转录激活所必需的。PI最近发现,小鼠红白血病细胞(MEL),一个红细胞的模型系统,缺乏cAMP依赖的蛋白激酶(A激酶),这是一种参与信号转导的酶,其成熟和激活红系基因的能力严重受损。核因子-E2的结合也存在异常。初步实验表明,A-激酶通过磷酸化p45和调节p45和p18的复合体的形成来调节核因子-E2。这项拨款中的实验将进一步检验这一点。通过确定哪些氨基酸被磷酸化,以了解这种磷酸化是否发生在红细胞成熟过程中,以及确定P45的这种磷酸化是否改变了它与p18的络合物形成并改变了核因子-E2激活红系基因的能力,将通过A激酶对P45的磷酸化进行研究。接下来的一系列实验将检查与核因子-E2相互作用的蛋白质,并观察这些相互作用是否会改变其功能。这项研究的结果将增加我们对核因子-E2功能调节的了解,并确定A-激酶在红细胞成熟过程中的作用。他们还将提供有关该酶在信号转导中的一般功能的信息。***
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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