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Mechanism of interferon action: structure of the mouse PKR gene encoding the interferon-inducible RNA-dependent protein kinase.

作者信息

Tanaka H, Samuel C E

机构信息

Department of Biological Sciences, University of California, Santa Barbara 93106.

出版信息

Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7995-9. doi: 10.1073/pnas.91.17.7995.

DOI:10.1073/pnas.91.17.7995
PMID:7914700
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC44531/
Abstract

The gene for the RNA-dependent eIF-2 alpha protein kinase (PKR) was isolated from mouse genomic DNA and characterized. The mouse PKR gene contains 16 exons and spans about 28 kilobase pairs. Exon 1 is untranslated; the AUG translation initiation site is located early in the second exon. Exon 16 includes the UAG translation termination site. ATTAAA polyadenylylation signal, and a putative TA rather than CA 3' cleavage site. Primer extension analysis determined one major as well as multiple minor transcription initiation sites; the major site was 159 bp upstream of the translation initiation site. The complete cDNA of mouse PKR is, therefore, 2334 bp in length excluding the 3' poly(A)+ tail. The PKR gene 5' flanking region was a functional promoter in interferon-treated, transfected cells as measured with chloramphenicol acetyltransferase as the reporter gene. Sequence analysis of the 5' flanking region disclosed numerous potential binding sites for transcription factors including both an ISRE element and a GAS element involved in interferon inducibility; Ets, Myb, MyoD, and E2F sites commonly associated with growth control regulation and differentiation; and NF-kappa B-like sites as well as sites for two types of interleukin 6-activated factors, NF-IL6 and APRF, often associated with acute-phase, immune, and inflammatory response genes.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/44531/ebf708c71b49/pnas01139-0175-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/44531/ebf708c71b49/pnas01139-0175-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/44531/ebf708c71b49/pnas01139-0175-a.jpg

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本文引用的文献

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Proc Natl Acad Sci U S A. 1993 May 1;90(9):4314-8. doi: 10.1073/pnas.90.9.4314.
2
The Ets family of transcription factors.Ets转录因子家族。
Eur J Biochem. 1993 Jan 15;211(1-2):7-18. doi: 10.1007/978-3-642-78757-7_2.
3
Translational regulation by the interferon-induced double-stranded-RNA-activated 68-kDa protein kinase.
乙醇对PKR信号通路的上调呈现出与发病年龄相关的关系。
Alcohol Clin Exp Res. 2016 Nov;40(11):2320-2328. doi: 10.1111/acer.13209. Epub 2016 Sep 20.
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Editing of Cellular Self-RNAs by Adenosine Deaminase ADAR1 Suppresses Innate Immune Stress Responses.腺苷脱氨酶ADAR1对细胞自身RNA的编辑可抑制先天性免疫应激反应。
J Biol Chem. 2016 Mar 18;291(12):6158-68. doi: 10.1074/jbc.M115.709014. Epub 2016 Jan 27.
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Increased expression of the dsRNA-activated protein kinase PKR in breast cancer promotes sensitivity to doxorubicin.dsRNA 激活蛋白激酶 PKR 在乳腺癌中的表达增加可提高对阿霉素的敏感性。
PLoS One. 2012;7(9):e46040. doi: 10.1371/journal.pone.0046040. Epub 2012 Sep 24.
6
Geranylgeranylacetone has anti-hepatitis C virus activity via activation of mTOR in human hepatoma cells.香叶基丙酮通过激活人肝癌细胞中的 mTOR 发挥抗丙型肝炎病毒活性。
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Chromosomal assignment of the interferon-inducible double-stranded RNA-dependent protein kinase (PRKR) to human chromosome 2p21-p22 and mouse chromosome 17 E2.
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