Inhibition of Nuclear Receptor Signalling by Poly(ADP-Ribose) Polymerase
Inhibition of Nuclear Receptor Signalling by Poly(ADP-Ribose) Polymerase
复制标题
聚 (ADP-核糖) 聚合酶对核受体信号传导的抑制
DOI：
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发表时间：
1999
影响因子：
5.3
通讯作者：
K. Hashizume
中科院分区：
文献类型：
--
作者：
T. Miyamoto;T. Kakizawa;K. Hashizume
哺乳动物多聚ADP-核糖聚合酶(PARP)是一种核染色质相关蛋白，其分子质量为114 kDa，催化ADP-核糖单位从NAD+向位于染色质内的核蛋白转移。我们在此报告了PARP作为核受体信号调节器的一种新特性的鉴定。PARP直接与维甲酸X受体(RXR)结合，并通过RXR和甲状腺激素受体(TR)的异源二聚体抑制配体依赖的转录活性。相互作用表面位于RXRα的DNA结合区。凝胶位移分析表明，PARP与反应元件上的tr-RXR异源二聚体结合。在瞬时转染实验中，野生型PARP的过表达选择性地阻断了核受体的功能，而酶缺陷突变体PARP没有表现出明显的抑制作用，这表明聚腺苷二磷酸核糖基的酶活性在核受体对基因的调控中起着重要的作用。此外，PARP与Gal4 DNA结合区的融合抑制了含有Gal4结合位点的启动子的转录活性。因此，当PARP被招募到启动子上时，它具有转录抑制活性。这些结果表明，聚(ADP-核糖基)是基因转录中的负辅助因子，调节核受体超家族的一个成员。
ABSTRACT Mammalian poly(ADP-ribose) polymerase (PARP) is a nuclear chromatin-associated protein with a molecular mass of 114 kDa that catalyzes the transfer of ADP-ribose units from NAD+ to nuclear proteins that are located within chromatin. We report here the identification of a novel property of PARP as a modulator of nuclear receptor signalling. PARP bound directly to retinoid X receptors (RXR) and repressed ligand-dependent transcriptional activities mediated by heterodimers of RXR and thyroid hormone receptor (TR). The interacting surface is located in the DNA binding domain of RXRα. Gel shift assays demonstrated that PARP bound to TR-RXR heterodimers on the response element. Overexpression of wild-type PARP selectively blocked nuclear receptor function in transient transfection experiments, while enzyme-defective mutant PARP did not show significant inhibition, suggesting that the essential role of poly(ADP-ribosyl) enzymatic activity is in gene regulation by nuclear receptors. Furthermore, PARP fused to the Gal4 DNA binding domain suppressed the transcriptional activity of the promoter harboring the Gal4 binding site. Thus, PARP has transcriptional repressor activity when recruited to the promoter. These results indicates that poly(ADP-ribosyl)ation is a negative cofactor in gene transcription, regulating a member of the nuclear receptor superfamily.
核受体辅阻遏物（N-CoR）表达水平对视黄酸受体介导的抑制的不同影响支持动态调节的辅阻遏物复合物的存在。
DOI：
10.1210/mend.11.6.0018
发表时间：
1997
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Soderstrom,M;Vo,A;Heinzel,T;Lavinsky,RM;Yang,WM;Seto,E;Peterson,DA;Rosenfeld,MG;Glass,CK
通讯作者：
Glass,CK
聚（ADP-核糖）聚合酶催化结构域和糖皮质激素受体 DNA 结合结构域之间融合蛋白的表达和表征。
影响因子：
3.1
作者：
Rosenthal,D;Hong,T;Cherney,B;Zhang,S;Shima,T;Danielsen,M;Smulson,M
通讯作者：
Smulson,M
DOI：
10.1073/pnas.95.7.3867
发表时间：
1998-03-31
影响因子：
11.1
作者：
Szabó, C;Virág, L;Kun, E
通讯作者：
Kun, E