Poly (ADP-ribose) polymerase is involved in PMA-induced activation of HIV-1 in U1 cells by modulating the LTR function.
Poly (ADP-ribose) polymerase is involved in PMA-induced activation of HIV-1 in U1 cells by modulating the LTR function.
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聚 (ADP-核糖) 聚合酶通过调节 LTR 功能参与 U1 细胞中 PMA 诱导的 HIV-1 激活。
DOI：
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发表时间：
1999
期刊：
影响因子：
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通讯作者：
K. Yoshihara
中科院分区：
文献类型：
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作者：
M. Kameoka;Y. Tanaka;K. Ota;A. Itaya;K. Yoshihara
佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的HIV-1在U1细胞中的产生被聚（ADP-核糖）聚合酶（PARP）抑制剂显著抑制。北方印迹分析显示PARP抑制剂在转录水平上抑制病毒的产生。为了研究PARP对HIV-1基因转录调控的影响，我们将含有HIV-1-LTR促进的荧光素酶基因的报告质粒转染到L-1210细胞克隆中，这些细胞克隆表达不同程度降低的PARP水平。在野生型L-1210细胞中，LTR促进的荧光素酶基因的表达被PMA刺激约4倍，而PMA依赖性反应在突变型细胞中几乎被消除，其仅表达野生型细胞的8%的PARP。PARP含量降低对HIV-1-LTR功能的影响也在人野生型细胞Jurkat和J111中得到证实，Jurkat和J111用报告质粒和表达PARP反义RNA的质粒共转染：通过表达反义RNA下调细胞中的PARP显著抑制Jurkat和J111细胞中报告质粒的PMA依赖性LTR功能。已知NF-κ B介导U1细胞中PMA诱导的HIV-1活化，发现其在PMA处理的U1细胞中活化约5倍。出乎意料的是，PARP抑制剂没有抑制而是刺激（约2倍）NF-κ B活化。结合这些结果以及尽管细胞中活化的NF-κ B水平非常高，但PARP缺陷突变细胞中LTR功能最小的发现，我们认为PARP除了活化的NF-κ B之外，对HIV-1 LTR的功能也是必不可少的。
Phorbol 12-myristate 13-acetate (PMA)-induced HIV-1 production in U1 cells was markedly suppressed by inhibitors of poly (ADP-ribose) polymerase (PARP). Northern blot analysis revealed that the PARP-inhibitors suppressed the virus production at a level of transcription. In order to examine the effect of PARP on transcriptional regulation of HIV-1 genes, we transfected a reporter plasmid containing HIV-1-LTR-promoted luciferase gene to L-1210 cell clones, which expressed varying decreased level of PARP. In wild type L-1210 cells, the expression of LTR-promoted luciferase gene was stimulated approximately 4-fold in response to PMA, whereas the PMA-dependent response was almost abolished in mutant cells, which expressed only 8% of PARP of the wild type cells. The effect of decrease in PARP content on the function of HIV-1-LTR was confirmed also in human wild type cells, Jurkat and J111, which were co-transfected with the reporter plasmid and a plasmid expressing a PARP-antisense RNA: Down-regulation of PARP in the cells by the expression of the antisense RNA significantly suppressed the PMA-dependent, LTR-function of the reporter plasmid in both Jurkat and J111 cells. NF-kappaB, which is known to mediate the PMA-induced activation of HIV-1 in U1 cells, was found to be activated approximately 5-fold in PMA-treated U1 cells. PARP-inhibitor, unexpectedly, did not suppress but rather stimulated (approximately 2-fold) the NF-kappaB activation. Combining the results with the finding that the LTR-function was minimum in a PARP-defective mutant cells in spite of a very high level of the activated NF-kappaB in the cells, we suggest that PARP, in addition to activated NF-kappaB, is essential for the function of HIV-1 LTR.
TFIIF 是一种基础真核转录因子，是聚 (ADP-核糖基) 化的底物。
DOI：
10.1042/bj3240249
发表时间：
1997
期刊：
The Biochemical journal
影响因子：
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作者：
Rawling,JM;Alvarez-Gonzalez,R
通讯作者：
Alvarez-Gonzalez,R