2,3,7,8-Tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymerase (TiPARP, ARTD14) is a mono-ADP-ribosyltransferase and repressor of aryl hydrocarbon receptor transactivation.
2,3,7,8-Tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymerase (TiPARP, ARTD14) is a mono-ADP-ribosyltransferase and repressor of aryl hydrocarbon receptor transactivation.
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DOI：
10.1093/nar/gks1337
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发表时间：
2013-02-01
影响因子：
14.9
通讯作者：
Matthews J
中科院分区：
文献类型：
--
作者：
MacPherson L;Tamblyn L;Rajendra S;Bralha F;McPherson JP;Matthews J
2，3，7，8-四氯二苯并-对-二恶英（TCDD）诱导的聚（ADP-核糖）聚合酶（TiPARP/ARTD 14）是PARP家族的成员，并且由芳烃受体（AHR）调节;然而，对TiPARP功能知之甚少。在这项研究中，我们研究了TiPARP的催化功能，并确定其在AHR反式激活中的作用。我们观察到TiPARP表现出自身单ADP核糖基转移酶活性和核糖基化的核心组蛋白。RNAi介导的T-47 D乳腺癌和HuH-7肝癌细胞中TiPARP的敲低增加了TCDD依赖性细胞色素P450 1A 1（CYP 1A 1）和CYP 1B 1信使RNA（mRNA）的表达水平以及AHR向两种基因的募集。TiPARP的过表达降低了CYP 1A 1报告基因活性的AHR依赖性增加，而AHR的过表达可恢复CYP 1A 1报告基因活性，但芳烃受体核转位蛋白的过表达不能恢复CYP 1A 1报告基因活性。缺失和突变研究表明，TiPARP介导的AHR抑制需要锌指结构域和催化结构域。TiPARP和AHR共定位于细胞核中，直接相互作用，并且两者都响应于TCDD被招募到CYP 1A 1。Tiparp的过表达增强，而RNAi介导的Tiparp敲低降低TCDD依赖的AHR蛋白水解降解。与野生型对照相比，Tiparp-/-小鼠胚胎成纤维细胞中AHR靶基因的TCDC依赖性诱导增强。我们的研究结果表明，TiPARP是一个单ADP-核糖基转移酶和AHR的转录抑制因子，揭示了一个新的负反馈环AHR信号。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP-ribose) polymerase (TiPARP/ARTD14) is a member of the PARP family and is regulated by the aryl hydrocarbon receptor (AHR); however, little is known about TiPARP function. In this study, we examined the catalytic function of TiPARP and determined its role in AHR transactivation. We observed that TiPARP exhibited auto-mono-ADP-ribosyltransferase activity and ribosylated core histones. RNAi-mediated knockdown of TiPARP in T-47D breast cancer and HuH-7 hepatoma cells increased TCDD-dependent cytochrome P450 1A1 (CYP1A1) and CYP1B1 messenger RNA (mRNA) expression levels and recruitment of AHR to both genes. Overexpression of TiPARP reduced AHR-dependent increases in CYP1A1-reporter gene activity, which was restored by overexpression of AHR, but not aryl hydrocarbon receptor nuclear translocator. Deletion and mutagenesis studies showed that TiPARP-mediated inhibition of AHR required the zinc-finger and catalytic domains. TiPARP and AHR co-localized in the nucleus, directly interacted and both were recruited to CYP1A1 in response to TCDD. Overexpression of Tiparp enhanced, whereas RNAi-mediated knockdown of TiPARP reduced TCDD-dependent AHR proteolytic degradation. TCDD-dependent induction of AHR target genes was enhanced in Tiparp−/− mouse embryonic fibroblasts compared with wildtype controls. Our findings show that TiPARP is a mono-ADP-ribosyltransferase and a transcriptional repressor of AHR, revealing a novel negative feedback loop in AHR signalling.
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影响因子：
4.8
作者：
Aguiar, RCT;Takeyama, K;Shipp, MA
通讯作者：
Shipp, MA
影响因子：
5.3
作者：
Karchner, Sibel I.;Jenny, Matthew J.;Hahn, Mark E.
通讯作者：
Hahn, Mark E.
影响因子：
11.4
作者：
García-Salcedo, JA;Gijón, P;Pays, E
通讯作者：
Pays, E
DOI：
10.1006/bbrc.2001.5987
发表时间：
2001-11-30
影响因子：
3.1
作者：
Ma, Q;Baldwin, KT;Dong, LQ
通讯作者：
Dong, LQ
影响因子：
8.8
作者：
Ma, Q;Baldwin, KT
通讯作者：
Baldwin, KT