HiNF-P Directly Links the Cyclin E/CDK2/p220NPAT Pathway to Histone H4 Gene Regulation at the G1/S Phase Cell Cycle Transition

Angela Miele; Corey D. Braastad; William F. Holmes; Partha Mitra; Ricardo Medina; Ronglin Xie; Sayyed K. Zaidi; Xin Ye; Yue Wei; J. Wade Harper; Andre J. van Wijnen; Janet L. Stein; Gary S. Stein

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HiNF-P Directly Links the Cyclin E/CDK2/p220NPAT Pathway to Histone H4 Gene Regulation at the G1/S Phase Cell Cycle Transition

机译：HINF-P在G1 / S期间细胞周期转换下将Cyclin E / CDK2 / P220NPAT路线直接链接到组蛋白H4基因调节

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Genome replication in eukaryotic cells necessitates the stringent coupling of histone biosynthesis with the onset of DNA replication at the G₁/S phase transition. A fundamental question is the mechanism that links the restriction (R) point late in G₁ with histone gene expression at the onset of S phase. Here we demonstrate that HiNF-P, a transcriptional regulator of replication-dependent histone H4 genes, interacts directly with p220NPAT, a substrate of cyclin E/CDK2, to coactivate histone genes during S phase. HiNF-P and p220 are targeted to, and colocalize at, subnuclear foci (Cajal bodies) in a cell cycle-dependent manner. Genetic or biochemical disruption of the HiNF-P/p220 interaction compromises histone H4 gene activation at the G₁/S phase transition and impedes cell cycle progression. Our results show that HiNF-P and p220 form a critical regulatory module that directly links histone H4 gene expression at the G₁/S phase transition to the cyclin E/CDK2 signaling pathway at the R point.

机译：真核细胞中的基因组复制需要组蛋白生物合成的严格偶联，在G <亚> 1 / S期转变处的DNA复制开始。基本问题是将Lig in G _{1 在S期开始时将限制（R）点与组蛋白基因表达联系起来的机制。在这里，我们证明了HinF-P，复制依赖性组蛋白H4基因的转录调节剂，直接用p220 npat ，细胞周期蛋白E / cdk2的底物相互作用，以在S期间共同激活组蛋白基因。 HINF-P和P220以细胞周期依赖性方式靶向，并以亚核焦点（CAJAL体）分开。 HINF-P / P220相互作用的遗传或生化破坏损害了G _{1 的相转变处的组蛋白H4基因活化，并阻碍了细胞周期进展。我们的结果表明，HinF-P和P220形成了一个关键调节模块，其直接将组蛋白H4基因表达直接将G _{1 / S期转移到R点处的Cyclin E / CDK2信号通路。}}}

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《Molecular and Cellular Biology》 |2005年第14期|共14页
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Angela Miele; Corey D. Braastad; William F. Holmes; Partha Mitra; Ricardo Medina; Ronglin Xie; Sayyed K. Zaidi; Xin Ye; Yue Wei; J. Wade Harper; Andre J. van Wijnen; Janet L. Stein; Gary S. Stein;
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中图分类细胞生物学;
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1. The Cyclin E/Cdk2 Substrate p220NPAT Is Required for S-Phase Entry, Histone Gene Expression, and Cajal Body Maintenance in Human Somatic Cells [J] . Xin Ye, Yue Wei, Grzegorz Nalepa, Molecular and Cellular Biology . 2003,第23期

机译：细胞周期蛋白E / Cdk2底物p220NPAT是人体细胞S期进入，组蛋白基因表达和Cajal体维持所必需的
2. Identification of HiNF-P, a Key Activator of Cell Cycle-Controlled Histone H4 Genes at the Onset of S Phase [J] . Partha Mitra, Rong-Lin Xie, Ricardo Medina, Molecular and Cellular Biology . 2003,第22期

机译：鉴定HiNF-P，S期开始时细胞周期控制的组蛋白H4基因的关键激活因子
3. The integrated activities of IRF-2 (HiNF-M), CDP/cut (HiNF-D) and H4TF-2 (HiNF-P) regulate transcription of a cell cycle controlled human histone H4 gene: mechanistic differences between distinct H4 genes. [J] . Aziz F, van-Wijnen AJ, Vaughan PS, Molecular biology reports . 1998,第1期

机译：IRF-2（HiNF-M），CDP / cut（HiNF-D）和H4TF-2（HiNF-P）的整合活性调节细胞周期控制的人类组蛋白H4基因的转录：不同H4基因之间的机制差异。
4. Top Down Mass Spectrometric Analyses of Histone H4 in Human Cancer Cells and Modification Dynamics During the Cell Cycle [C] . James J. Pesavento, Courtney R. Bullock, Neil L. Kelleher, ASMS Conference on Mass Spectrometry and Allied Topics . 2006

机译：在细胞周期中的人癌细胞中组蛋白H4的全部质谱分析和修饰动力学
5. Regulation of late G1 to S phase cell cycle progression: The role of cyclin-dependent kinase 2. [D] . Keenan, Susan Margaret. 2001

机译：晚期G1到S期细胞周期进程的调节：细胞周期蛋白依赖性激酶2的作用。
6. HiNF-P Directly Links the Cyclin E/CDK2/p220NPAT Pathway to Histone H4 Gene Regulation at the G1/S Phase Cell Cycle Transition [O] . Angela Miele, Corey D. Braastad, William F. Holmes, 2005

机译：HiNF-P在G1 / S期细胞周期转换中直接将细胞周期蛋白E / CDK2 / p220NPAT途径与组蛋白H4基因调控联系起来
7. HiNF-P Directly Links the Cyclin E/CDK2/p220NPAT Pathway to Histone H4 Gene Regulation at the G1/S Phase Cell Cycle Transition [O] . Miele, Angela, Braastad, Corey D., Holmes, William F., 2005

机译：HiNF-P在G1 / S期细胞周期转换中直接将细胞周期蛋白E / CDK2 / p220NPAT途径与组蛋白H4基因调控联系起来
8. Regulation of Ubiquitin Mediated Proteolysis of G1 Cyclins and the CDK Inhibitor p27 by the Cullin Gene Family in Normal Tumorigenic Human Breast Cells [R] . McCarville, J. , Xiong, Y. 2001

机译：正常致瘤人乳腺细胞中Cullin基因家族对泛素介导的G1细胞周期蛋白和CDK抑制剂p27蛋白水解的调节

HiNF-P Directly Links the Cyclin E/CDK2/p220NPAT Pathway to Histone H4 Gene Regulation at the G1/S Phase Cell Cycle Transition

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