MECHANISM OF SELENOPROTEIN SYNTHESIS IN EUKARYOTES
真核生物硒蛋白合成机制
基本信息
- 批准号:6145482
- 负责人:
- 金额:$ 4.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-08-01 至 2000-07-31
- 项目状态:已结题
- 来源:
- 关键词:NAD(P)H oxidoreductase RNA binding protein Xenopus oocyte animal tissue cysteine eukaryote gene mutation genetic library genetic mapping genetic translation messenger RNA nucleic acid sequence nucleic acid structure protein biosynthesis protein localization protein structure function ribosomes selenated sulfur aminoacid selenium selenoprotein thioredoxin tissue /cell culture transfection translation factor yeast two hybrid system
项目摘要
Selenium is an essential trace element which has provoked considerable
interest due to identification of a growing number of enzymes that
contain the amino acid, selenocysteine. A number of these enzymes
catalyze reactions that are critical to health or life. The first
identified mammalian selenoenzymes, the glutathione peroxidases,
catalyze detoxification of peroxides and thus, protection from oxidative
stress. Another class of redox selenoenzymes, the thioredoxin
reductases, play roles in proper transcription factor folding and
generating reducing equivalents for deoxribonucleotide synthesis. The
iodothyronine deiodinases, also selenoenzymes, catalyze thyroid hormone
activation and inactivation and are thus essential to regulation of the
many functions of thyroid hormone. Additional classes of selenoproteins
are being discovered, with evidence for intruiging and important
functions in many biological processes. In addition to cellular
functions, a growing body of data is accumulating implicating selenium
in the pathology of a number of viruses. Selenium status appears to
affect HIV replication and the progression of AIDS, host selection for
virulent strains of Coxsackie virus, and sensitivity to apoptosis in
Molluscum contagiosum poxvirus infection. Studies have also implicated
selenium in protection from lung, colon, and prostate cancer.
Incorporation of selenocysteine into proteins requires a novel
translation step in which UGA specifies selenocysteine insertion.
Selenoproteins are found in eukaryotes, eubacteria, and archae, but the
mechanisms of incorporation are distinct. While much is known about
selenocysteine incorporation in bacteria, our knowledge about the
eukaryotic process, where some of the more intriguing mechanistic
questions lie, has lagged behind. The focus of this proposal is to
further our understanding of the process of selenocysteine incorporation
in eukaryotes, through investigation of the RNA and protein factors
mediating this process, and their interactions. This includes
continuing structural studies of the RNA sequences that direct
selenocysteine incorporation, and intriguingly, some recently identified
polymorphisms in these structures that appear to have consequences for
human disease. We are also focusing on identification and
characterization of the protein factors that interact with these RNAs
to mediate incorporation at the ribosome. Finally, proposed studies
include investigation of the functions and mechanisms of regulation of
newly identified selenoproteins.
硒是一种必需的微量元素,它已经引发了相当大的
由于鉴定出越来越多的酶
含有氨基酸,硒半胱氨酸。许多这样的酶
催化对健康或生命至关重要的反应。第一
确定了哺乳动物的硒酶,谷胱甘肽过氧化物酶,
催化过氧化物解毒,从而保护免受氧化
压力。另一类氧化还原硒酶--硫氧还蛋白
还原酶,在适当的转录因子折叠和
生成用于脱氧核苷酸合成的还原等价物。这个
碘甲腺原氨酸脱碘酶,也是硒酶,催化甲状腺激素
激活和失活,因此对调节
甲状腺激素的多种功能。其他类型的硒蛋白
正在被发现,有证据表明入侵和重要
在许多生物过程中发挥作用。除了蜂窝
函数,越来越多的数据正在积累与硒有关的信息
在一些病毒的病理中。硒的状态似乎是
影响艾滋病毒复制和艾滋病进展的宿主选择
柯萨奇病毒强毒株及其对细胞凋亡的敏感性
传染性软体肿痘病毒感染。研究还表明,
硒对肺癌、结肠癌和前列腺癌的保护作用。
将硒半胱氨酸掺入蛋白质需要一种新的
翻译步骤,其中UGA指定硒半胱氨酸插入。
硒蛋白存在于真核生物、真细菌和古生物中,但
公司成立的机制是不同的。虽然很多人都知道
在细菌中掺入硒半胱氨酸,我们对
真核过程中,一些更耐人寻味的机制
问题是谎言,已经落后了。这项提议的重点是
加深对硒半胱氨酸掺入过程的理解
在真核生物中,通过对RNA和蛋白质因子的研究
调解这一过程,以及他们之间的互动。这包括
对RNA序列的持续结构研究
硒半胱氨酸的掺入,有趣的是,最近发现了一些
这些结构中的多态似乎会对
人类疾病。我们还将重点放在识别和
与这些RNA相互作用的蛋白质因子的特性
以调节核糖体的整合。最后,提出了研究建议。
包括对调节的功能和机制的研究
新鉴定的硒蛋白。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Marla J Berry其他文献
Insights into the hierarchy of selenium incorporation
对硒掺入层次结构的洞察
- DOI:
10.1038/ng1105-1162 - 发表时间:
2005-11-01 - 期刊:
- 影响因子:29.000
- 作者:
Marla J Berry - 通讯作者:
Marla J Berry
Marla J Berry的其他文献
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{{ truncateString('Marla J Berry', 18)}}的其他基金
Integrative Center for Precision Nutrition and Human Health
精准营养与人类健康综合中心
- 批准号:
10799440 - 财政年份:2022
- 资助金额:
$ 4.34万 - 项目类别:
Integrative Center for Precision Nutrition and Human Health
精准营养与人类健康综合中心
- 批准号:
10594442 - 财政年份:2022
- 资助金额:
$ 4.34万 - 项目类别:
RESEARCH DESIGN, BIOSTATISTICS AND RESEARCH ETHICS CORE
研究设计、生物统计学和研究伦理核心
- 批准号:
9360806 - 财政年份:2015
- 资助金额:
$ 4.34万 - 项目类别:
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