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在经干扰素处理的小鼠L细胞的无细胞体系中,蛋白质P1和真核起始因子2α的双链RNA依赖性磷酸化与蛋白质合成抑制不相关。

Double-stranded RNA-dependent phosphorylation of protein P1 and eukaryotic initiation factor 2 alpha does not correlate with protein synthesis inhibition in a cell-free system from interferon-treated mouse L cells.

作者信息

Jacobsen H, Epstein D A, Friedmann R M, Safer B, Torrence P F

出版信息

Proc Natl Acad Sci U S A. 1983 Jan;80(1):41-5. doi: 10.1073/pnas.80.1.41.

DOI:10.1073/pnas.80.1.41
PMID:6185959
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC393305/
Abstract

The double-stranded RNAs (I)n X (C)n and (A)n X (dUfl)n (dUfl is 2'-fluoro-2'-deoxyuridylic acid) have been compared as inhibitors of translation in cell-free systems from interferon-treated mouse L cells and from rabbit reticulocytes. In the interferon-treated mouse L-cell system, both double-stranded RNAs stimulated kinase activity, leading to phosphorylation of protein P1 and eukaryotic initiation factor 2 alpha (eIF-2 alpha), but only (1)n X (C)n activated the (2'-5')-oligoadenylate synthetase. Moreover, in this system, (I)n X (C)n, but not (A)n X (dUfl)n, inhibited translation. Both (A)n X (dUfl)n and (I)n X (C)n also activated the rabbit reticulocyte kinase to phosphorylate protein P1 and eIF-2 alpha, but, in contrast to mouse L-cell systems, both (A)n X (dUfl)n and (I)n X (C)n were potent inhibitors of translation in reticulocyte lysates. These results indicate that protein P1 and eIF-2 alpha phosphorylation are not sufficient to cause inhibition of protein synthesis in interferon-treated mouse L-cell extracts. They further suggest that protein synthesis inhibition by (I)n X (C)n in extracts of interferon-treated L cells correlates better with activation of (2'-5')-oligoadenylate synthetase than with activation of the protein P1 and eIF-2 alpha kinase.

摘要

已对双链RNA(I)nX(C)n和(A)nX(dUfl)n(dUfl为2'-氟-2'-脱氧尿苷酸)作为来自经干扰素处理的小鼠L细胞和兔网织红细胞的无细胞系统中翻译抑制剂进行了比较。在经干扰素处理的小鼠L细胞系统中,两种双链RNA均刺激激酶活性,导致蛋白质P1和真核起始因子2α(eIF-2α)磷酸化,但只有(I)nX(C)n激活(2'-5')-寡腺苷酸合成酶。此外,在该系统中,(I)nX(C)n而非(A)nX(dUfl)n抑制翻译。(A)nX(dUfl)n和(I)nX(C)n均还激活兔网织红细胞激酶使蛋白质P1和eIF-2α磷酸化,但与小鼠L细胞系统相反,(A)nX(dUfl)n和(I)nX(C)n在网织红细胞裂解物中均是有效的翻译抑制剂。这些结果表明,蛋白质P1和eIF-2α磷酸化不足以导致经干扰素处理的小鼠L细胞提取物中蛋白质合成的抑制。它们进一步表明,经干扰素处理的L细胞提取物中(I)nX(C)n对蛋白质合成的抑制与(2'-5')-寡腺苷酸合成酶的激活比与蛋白质P1和eIF-2α激酶的激活相关性更好。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5036/393305/58ea0c904892/pnas00627-0059-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5036/393305/6a6dcda7c422/pnas00627-0057-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5036/393305/3e2a4ebb6743/pnas00627-0058-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5036/393305/88cdcc47f8b8/pnas00627-0058-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5036/393305/58ea0c904892/pnas00627-0059-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5036/393305/6a6dcda7c422/pnas00627-0057-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5036/393305/3e2a4ebb6743/pnas00627-0058-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5036/393305/88cdcc47f8b8/pnas00627-0058-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5036/393305/58ea0c904892/pnas00627-0059-a.jpg

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本文引用的文献

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Indirect inactivation of eukaryotic initiation factor 2 in reticulocyte lysate by selenite.
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Chromatographic assay on DEAE-cellulose for (2'-5')-oligo(A) synthesis in cell extracts.
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5'-O-Monophosphoryladenylyl(2' goes to 5')adenylyl(2' goes to 5')adenosine is an antagonist of the action of 5'-O-triphosphoryladenylyl-(2' goes to 5')adenylyl(2' goes to 5')adenosine and double-stranded RNA.5'-O-单磷酸腺苷(2'至5')腺苷(2'至5')腺苷是5'-O-三磷酸腺苷(2'至5')腺苷(2'至5')腺苷和双链RNA作用的拮抗剂。
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Adenovirus inhibition of cellular protein synthesis is prevented by the drug 2-aminopurine.药物2-氨基嘌呤可防止腺病毒对细胞蛋白质合成的抑制。
Proc Natl Acad Sci U S A. 1990 Sep;87(18):7115-9. doi: 10.1073/pnas.87.18.7115.
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