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1
The Rep68 protein of adeno-associated virus type 2 stimulates expression of the platelet-derived growth factor B c-sis proto-oncogene.2型腺相关病毒的Rep68蛋白刺激血小板衍生生长因子B c-sis原癌基因的表达。
J Virol. 1996 Jul;70(7):4783-6. doi: 10.1128/JVI.70.7.4783-4786.1996.
2
Negative regulation of the adeno-associated virus (AAV) P5 promoter involves both the P5 rep binding site and the consensus ATP-binding motif of the AAV Rep68 protein.腺相关病毒（AAV）P5启动子的负调控涉及P5 Rep结合位点和AAV Rep68蛋白的共有ATP结合基序。
J Virol. 1995 Nov;69(11):6787-96. doi: 10.1128/JVI.69.11.6787-6796.1995.
3
Roles of adeno-associated virus Rep protein and human chromosome 19 in site-specific recombination.腺相关病毒Rep蛋白和人类19号染色体在位点特异性重组中的作用。
J Virol. 2000 May;74(9):3953-66. doi: 10.1128/jvi.74.9.3953-3966.2000.
4
The Rep68 protein of adeno-associated virus type 2 increases RNA levels from the human cytomegalovirus major immediate early promoter.2型腺相关病毒的Rep68蛋白可提高人巨细胞病毒主要立即早期启动子的RNA水平。
Virology. 1997 Sep 15;236(1):167-76. doi: 10.1006/viro.1997.8724.
5
The adeno-associated virus type 2 regulatory proteins rep78 and rep68 interact with the transcriptional coactivator PC4.2型腺相关病毒调节蛋白rep78和rep68与转录共激活因子PC4相互作用。
J Virol. 1999 Jan;73(1):260-9. doi: 10.1128/JVI.73.1.260-269.1999.
6
High-level expression of adeno-associated virus (AAV) Rep78 or Rep68 protein is sufficient for infectious-particle formation by a rep-negative AAV mutant.腺相关病毒（AAV）Rep78或Rep68蛋白的高水平表达足以使rep阴性AAV突变体形成感染性颗粒。
J Virol. 1995 Nov;69(11):6880-5. doi: 10.1128/JVI.69.11.6880-6885.1995.
7
Binding sites for adeno-associated virus Rep proteins within the human genome.人类基因组中腺相关病毒Rep蛋白的结合位点。
J Virol. 1997 Mar;71(3):2528-34. doi: 10.1128/JVI.71.3.2528-2534.1997.
8
Selective cleavage of AAVS1 substrates by the adeno-associated virus type 2 rep68 protein is dependent on topological and sequence constraints.2型腺相关病毒rep68蛋白对AAVS1底物的选择性切割取决于拓扑结构和序列限制。
J Virol. 2000 Oct;74(19):8831-42. doi: 10.1128/jvi.74.19.8831-8842.2000.
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Identification of linear DNA sequences that specifically bind the adeno-associated virus Rep protein.鉴定与腺相关病毒Rep蛋白特异性结合的线性DNA序列。
J Virol. 1994 Aug;68(8):4988-97. doi: 10.1128/JVI.68.8.4988-4997.1994.
10
Analysis of adeno-associated virus (AAV) wild-type and mutant Rep proteins for their abilities to negatively regulate AAV p5 and p19 mRNA levels.分析腺相关病毒（AAV）野生型和突变型Rep蛋白对AAV p5和p19 mRNA水平进行负调控的能力。
J Virol. 1994 May;68(5):2947-57. doi: 10.1128/JVI.68.5.2947-2957.1994.

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Vaccinia virus as a subhelper for AAV replication and packaging.牛痘病毒作为 AAV 复制和包装的亚辅助病毒。
Mol Ther Methods Clin Dev. 2015 Nov 18;2:15044. doi: 10.1038/mtm.2015.44. eCollection 2015.
2
Adeno-associated virus Rep represses the human integration site promoter by two pathways that are similar to those required for the regulation of the viral p5 promoter.腺相关病毒 Rep 通过两条途径抑制人类整合位点启动子，这两条途径类似于调节病毒 p5 启动子所必需的途径。
J Virol. 2014 Aug;88(15):8227-41. doi: 10.1128/JVI.00412-14. Epub 2014 May 14.
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Transcriptional analysis of the adeno-associated virus integration site.腺相关病毒整合位点的转录分析
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4
Identification of cellular proteins that interact with the adeno-associated virus rep protein.鉴定与腺相关病毒rep蛋白相互作用的细胞蛋白。
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5
Stable secondary structure near the nicking site for adeno-associated virus type 2 Rep proteins on human chromosome 19.人19号染色体上2型腺相关病毒Rep蛋白切割位点附近的稳定二级结构。
J Virol. 2005 Mar;79(6):3544-56. doi: 10.1128/JVI.79.6.3544-3556.2005.
6
Studies of the mechanism of transactivation of the adeno-associated virus p19 promoter by Rep protein.腺相关病毒p19启动子经Rep蛋白反式激活机制的研究。
J Virol. 2002 Aug;76(16):8225-35. doi: 10.1128/jvi.76.16.8225-8235.2002.
7
Efficient integration of recombinant adeno-associated virus DNA vectors requires a p5-rep sequence in cis.重组腺相关病毒DNA载体的有效整合在顺式条件下需要一个p5-Rep序列。
J Virol. 2002 Jun;76(11):5411-21. doi: 10.1128/jvi.76.11.5411-5421.2002.
8
A genetic screen identifies a cellular regulator of adeno-associated virus.一项基因筛选鉴定出腺相关病毒的一种细胞调节因子。
Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14991-6. doi: 10.1073/pnas.261567198. Epub 2001 Dec 4.
9
Selective cleavage of AAVS1 substrates by the adeno-associated virus type 2 rep68 protein is dependent on topological and sequence constraints.2型腺相关病毒rep68蛋白对AAVS1底物的选择性切割取决于拓扑结构和序列限制。
J Virol. 2000 Oct;74(19):8831-42. doi: 10.1128/jvi.74.19.8831-8842.2000.
10
Mechanism of Rep-mediated adeno-associated virus origin nicking.Rep介导的腺相关病毒起源切口的机制。
J Virol. 2000 Sep;74(17):7762-71. doi: 10.1128/jvi.74.17.7762-7771.2000.

本文引用的文献

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Identification of a DNA-binding domain in the amino terminus of adeno-associated virus Rep proteins.腺相关病毒Rep蛋白氨基末端DNA结合结构域的鉴定。
J Virol. 1993 Feb;67(2):997-1005. doi: 10.1128/JVI.67.2.997-1005.1993.
2
Adeno-associated virus type 2 rep gene-mediated inhibition of basal gene expression of human immunodeficiency virus type 1 involves its negative regulatory functions.2型腺相关病毒rep基因介导的对1型人类免疫缺陷病毒基础基因表达的抑制涉及其负调控功能。
J Virol. 1994 Feb;68(2):1229-33. doi: 10.1128/JVI.68.2.1229-1233.1994.
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Identification of linear DNA sequences that specifically bind the adeno-associated virus Rep protein.鉴定与腺相关病毒Rep蛋白特异性结合的线性DNA序列。
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Adeno-associated virus (AAV) Rep proteins mediate complex formation between AAV DNA and its integration site in human DNA.腺相关病毒（AAV）的Rep蛋白介导AAV DNA与人DNA中其整合位点之间形成复合物。
Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5808-12. doi: 10.1073/pnas.91.13.5808.
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Down-regulation of the human c-fos and c-myc proto-oncogene promoters by adeno-associated virus Rep78.
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Prospects for the use of adeno-associated virus as a vector for human gene therapy.腺相关病毒作为人类基因治疗载体的应用前景。
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DNA-damaging agents greatly increase the transduction of nondividing cells by adeno-associated virus vectors.
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The regulatory rep protein of adeno-associated virus binds to sequences within the c-H-ras promoter.腺相关病毒的调节性Rep蛋白与c-H-ras启动子内的序列结合。
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Site-specific integration by adeno-associated virus is directed by a cellular DNA sequence.腺相关病毒的位点特异性整合由细胞DNA序列指导。
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The trans-inhibitory Rep78 protein of adeno-associated virus binds to TAR region DNA of the human immunodeficiency virus type 1 long terminal repeat.腺相关病毒的反式抑制蛋白Rep78与人类免疫缺陷病毒1型长末端重复序列的TAR区域DNA结合。
FEBS Lett. 1995 Jul 3;367(3):267-71. doi: 10.1016/0014-5793(95)00584-v.

2型腺相关病毒的Rep68蛋白刺激血小板衍生生长因子B c-sis原癌基因的表达。

The Rep68 protein of adeno-associated virus type 2 stimulates expression of the platelet-derived growth factor B c-sis proto-oncogene.

作者信息

Wonderling R S, Owens R A

机构信息

Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.

出版信息

J Virol. 1996 Jul;70(7):4783-6. doi: 10.1128/JVI.70.7.4783-4786.1996.

DOI:10.1128/JVI.70.7.4783-4786.1996
PMID:8676507
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC190417/
Abstract

Rep68 protein, encoded by adeno-associated virus type 2 (AAV), has been previously shown to bind to specific sequences within the viral genome and in human chromosome 19. The effect of AAV Rep protein on human cellular genes is of interest because AAV is being developed as a gene therapy vector. We have identified sequences related to the Rep recognition sequence in the AAV P5 promoter in or near the c-sis proto-oncogene and the genes coding for a hepatocyte glucose transporter, alpha-A-crystallin, and carcinoma marker GA733-1. The ability of Rep68 to bind to these sites was established by gel shift assays, and the effect of Rep68 on the expression of these genes was tested by semiquantitative reverse transcriptase PCR. Rep68 enhances the expression of the c-sis proto-oncogene, which codes for the B polypeptide of platelet-derived growth factor, a multifunctional growth factor that is involved in embryonic development, tissue regeneration, osteogenesis, fibrosis, atherosclerosis, and neoplasia.

摘要

由2型腺相关病毒（AAV）编码的Rep68蛋白，先前已显示可与病毒基因组内以及人类19号染色体上的特定序列结合。由于AAV正被开发为一种基因治疗载体，因此AAV Rep蛋白对人类细胞基因的影响备受关注。我们已经在c-sis原癌基因以及编码肝细胞葡萄糖转运蛋白、α-A-晶状体蛋白和癌标志物GA733-1的基因中或附近，鉴定出了与AAV P5启动子中Rep识别序列相关的序列。通过凝胶迁移试验确定了Rep68与这些位点结合的能力，并通过半定量逆转录酶PCR检测了Rep68对这些基因表达的影响。Rep68增强了c-sis原癌基因的表达，该基因编码血小板衍生生长因子的B多肽，血小板衍生生长因子是一种多功能生长因子，参与胚胎发育、组织再生、成骨、纤维化、动脉粥样硬化和肿瘤形成。