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E2F-2的克隆与特性分析,一种具有转录因子E2F生化特性的新型蛋白质。

Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F.

作者信息

Ivey-Hoyle M, Conroy R, Huber H E, Goodhart P J, Oliff A, Heimbrook D C

机构信息

Department of Cancer Research, Merck Research Laboratories, West Point, Pennsylvania 19486.

出版信息

Mol Cell Biol. 1993 Dec;13(12):7802-12. doi: 10.1128/mcb.13.12.7802-7812.1993.

DOI:10.1128/mcb.13.12.7802-7812.1993
PMID:8246995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC364852/
Abstract

E2F is a mammalian transcription factor that appears to play an important role in cell cycle regulation. While at least two proteins (E2F-1 and DP-1) with E2F-like activity have been cloned, studies from several laboratories suggest that additional homologs may exist. A novel protein with E2F-like properties, designated E2F-2, was cloned by screening a HeLa cDNA library with a DNA probe derived from the DNA binding domain of E2F-1 (K. Helin, J. A. Lees, M. Vidal, N. Dyson, E. Harlow, and A. Fattaey, Cell 70:337-350, 1992). E2F-2 exhibits overall 46% amino acid identity to E2F-1. Both the sequence and the function of the DNA and retinoblastoma gene product binding domains of E2F-1 are conserved in E2F-2. The DNA binding activity of E2F-2 is dramatically enhanced by complementation with particular sodium dodecyl sulfate-polyacrylamide gel electrophoresis-purified components of HeLa cell E2F, and anti-E2F-2 antibodies cross-react with components of purified HeLa cell E2F. These observations are consistent with a model in which E2F binds DNA as a heterodimer of two distinct proteins, and E2F-2 is functionally and immunologically related to one of these proteins.

摘要

E2F是一种哺乳动物转录因子,似乎在细胞周期调控中发挥重要作用。虽然已经克隆出至少两种具有E2F样活性的蛋白质(E2F-1和DP-1),但几个实验室的研究表明可能存在其他同源物。通过用源自E2F-1 DNA结合结构域的DNA探针筛选HeLa cDNA文库,克隆出一种具有E2F样特性的新型蛋白质,命名为E2F-2(K. 赫林、J. A. 李斯、M. 维达尔、N. 戴森、E. 哈洛和A. 法塔伊,《细胞》70:337 - 350,1992年)。E2F-2与E2F-1的氨基酸序列总体一致性为46%。E2F-1的DNA和视网膜母细胞瘤基因产物结合结构域的序列和功能在E2F-2中均保守。通过与HeLa细胞E2F的特定十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳纯化成分互补,E2F-2的DNA结合活性显著增强,并且抗E2F-2抗体与纯化的HeLa细胞E2F成分发生交叉反应。这些观察结果与一个模型一致,即E2F作为两种不同蛋白质的异二聚体结合DNA,并且E2F-2在功能和免疫方面与其中一种蛋白质相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140a/364852/a257f3aad6f0/molcellb00024-0621-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140a/364852/adf4ae404c8f/molcellb00024-0616-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140a/364852/fbb78e508730/molcellb00024-0619-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140a/364852/40a8c8963507/molcellb00024-0619-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140a/364852/97c2b18de602/molcellb00024-0620-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140a/364852/a257f3aad6f0/molcellb00024-0621-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140a/364852/adf4ae404c8f/molcellb00024-0616-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140a/364852/fbb78e508730/molcellb00024-0619-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140a/364852/40a8c8963507/molcellb00024-0619-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140a/364852/97c2b18de602/molcellb00024-0620-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140a/364852/a257f3aad6f0/molcellb00024-0621-a.jpg

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本文引用的文献

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Cell. 1993 May 7;73(3):499-511. doi: 10.1016/0092-8674(93)90137-f.
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Transcription factor E2F binds DNA as a heterodimer.转录因子E2F作为异二聚体与DNA结合。
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3525-9. doi: 10.1073/pnas.90.8.3525.
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Interactions of the p107 and Rb proteins with E2F during the cell proliferation response.细胞增殖反应过程中p107和Rb蛋白与E2F的相互作用。
人胰腺腺癌中E2F转录因子的预后及免疫浸润综合分析
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Low E2F2 activity is associated with high genomic instability and PARPi resistance.E2F2 活性低与基因组高度不稳定和 PARPi 耐药性相关。
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Serve as Potential Prognostic Biomarkers and Targets for Human Ovarian Cancer.作为人类卵巢癌潜在的预后生物标志物和靶点。
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