CRYSTALLOGRAPHIC STUDIES OF VIRAL CYCLINS AND CDK6
病毒细胞周期蛋白和 CDK6 的晶体学研究
基本信息
- 批准号:2837489
- 负责人:
- 金额:$ 12.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-12-01 至 2002-11-30
- 项目状态:已结题
- 来源:
- 关键词:Herpesvirus saimiri X ray crystallography bioimaging /biomedical imaging cell transformation crystallization cyclin dependent kinase cyclins enzyme complex enzyme structure human herpesvirus 8 protein isoforms protein purification protein structure protein structure function structural biology tissue /cell culture virus protein
项目摘要
In recent years, key enzymes that regulate cell cycle progression have
been identified and characterized extensively. The major transition of
the eucaryotic cell cycle are controlled by cyclin-dependent protein
kinases (CDKs) that exert their regulatory function by phosphorylation
of key proteins involved in cell cycle transitions. To ensure proper
timing and coordination of cell cycle events, CDK kinase activity is
tightly controlled by various mechanisms, such as activation of the
apoenzyme by complex formation with cyclins, activating and inhibiting
phosphorylations, and complex formation with inhibitory proteins. Not
surprisingly from their key role in cell cycle control, mutations and
overexpression of cyclins and CDKs have been reported to be oncogenic
events. The recent discovery of two proteins from oncogenic herpes
viruses that show close homology with human D-type cyclins supports
these observations. V-cyclin from herpesvirus saimiri (HVS) and k-
cyclin from Kaposi's sarcoma associated herpesvirus (KSHV) show 24
percent and 31 percent identity with human cyclin D1 and D3,
respectively. They associate with CDK4 and CDK6, resulting in strong
kinase activity toward retinoblastoma protein and histone H1. This high
level of unlicensed kinase activity most likely induces deregulation of
cell proliferation inherent to HVS and KSHV diseases. The sequence
homologies between viral cyclins and D-type cyclins and the similarities
in CDK activation make viral cyclins a good system to study activation
mechanisms of CDK4 and CDK6, that might lead to oncogenic events if not
properly controlled. Futhermore, KSHV is implicated in the development
of Kaposi's sarcoma, especially in AIDS patients. Hence, studies of the
two homologous viral cylclins may contribute to understanding the
pathogenesis and treatment of this disease.
The short term goal is to determine the three-dimensional structure of
v-cyclin. The long-term goal is to determine the structures of k-
cyclin, and CDK6 by x-ray crystallography and to study complexes of CDK6
with viral cyclins with the final aim of structure determination as
well. This information will help to understand the activation mechanism
of host cell CDKs by proteins from viruses that cause various diseases
including cancer.
近年来,调节细胞周期进程的关键酶已经被发现,
被广泛地识别和表征。 的重大转变
真核细胞周期由细胞周期蛋白依赖性蛋白控制
通过磷酸化发挥其调节功能的激酶(CDKs)
参与细胞周期转换的关键蛋白质。 以确保适当
细胞周期事件的时间和协调,CDK激酶活性是
受到各种机制的严格控制,例如激活
脱辅基酶通过与细胞周期蛋白形成复合物,激活和抑制
磷酸化和与抑制蛋白的复合物形成。 不
令人惊讶的是,它们在细胞周期控制、突变和
已经报道细胞周期蛋白和CDK的过表达是致癌的
事件 最近发现的两种致癌性疱疹蛋白
与人D型细胞周期蛋白显示出密切同源性的病毒支持
这些观察。 来自松鼠猴疱疹病毒(HVS)的V-细胞周期蛋白和k-
来自卡波西肉瘤相关疱疹病毒(KSHV)的细胞周期蛋白显示24
与人细胞周期蛋白D1和D3的同源性分别为10%和31%,
分别 它们与CDK 4和CDK 6缔合,导致强的
对视网膜母细胞瘤蛋白和组蛋白H1的激酶活性。 这种高
未经许可的激酶活性水平最可能诱导
HVS和KSHV疾病固有的细胞增殖。 序列
病毒细胞周期蛋白与D型细胞周期蛋白的同源性及其相似性
在CDK活化中使病毒周期蛋白成为研究活化的良好系统
CDK 4和CDK 6的机制,如果没有,可能导致致癌事件
适当控制。此外,KSHV与开发
尤其是艾滋病患者 因此,研究
两个同源的病毒细胞周期蛋白可能有助于理解
发病机制和治疗。
短期目标是确定的三维结构
v-cyclin。 长期目标是确定k-
细胞周期蛋白和CDK 6的X射线晶体学研究CDK 6的复合物
与病毒细胞周期蛋白的最终目的是结构确定,
好. 这些信息将有助于理解激活机制
引起各种疾病的病毒蛋白质对宿主细胞CDKs的作用
包括癌症
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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URSULA SCHULZE-GAHMEN其他文献
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{{ truncateString('URSULA SCHULZE-GAHMEN', 18)}}的其他基金
Targeting Tat/TAR interactions with the superelongation complex to develop novel treatments for HIV/AIDS
靶向 Tat/TAR 与超伸长复合物的相互作用,开发艾滋病毒/艾滋病的新疗法
- 批准号:
10304202 - 财政年份:2020
- 资助金额:
$ 12.65万 - 项目类别:
STRUCTURAL STUDIES OF THE DNA REPAIR PROTEINS OF THE RECFOR PATHWAY IN THERMUS T
热能 T 中 RECFOR 途径 DNA 修复蛋白的结构研究
- 批准号:
7180498 - 财政年份:2005
- 资助金额:
$ 12.65万 - 项目类别:
CRYSTALLOGRAPHIC STUDIES OF VIRAL CYCLINS AND CDK6
病毒细胞周期蛋白和 CDK6 的晶体学研究
- 批准号:
6328756 - 财政年份:1997
- 资助金额:
$ 12.65万 - 项目类别:
CRYSTALLOGRAPHIC STUDIES OF VIRAL CYCLINS AND CDK6
病毒细胞周期蛋白和 CDK6 的晶体学研究
- 批准号:
6475628 - 财政年份:1997
- 资助金额:
$ 12.65万 - 项目类别:
CRYSTALLOGRAPHIC STUDIES OF VIRAL CYCLINS AND CDK6
病毒细胞周期蛋白和 CDK6 的晶体学研究
- 批准号:
2440552 - 财政年份:1997
- 资助金额:
$ 12.65万 - 项目类别:
CRYSTALLOGRAPHIC STUDIES OF VIRAL CYCLINS AND CDK6
病毒细胞周期蛋白和 CDK6 的晶体学研究
- 批准号:
6124340 - 财政年份:1997
- 资助金额:
$ 12.65万 - 项目类别:
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