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首页> 外文期刊>Gene expression >Transcription coactivator PRIP, the peroxisome proliferator-activated receptor (PPAR)-interacting protein, is redundant for the function of nuclear receptors PParalpha and CAR, the constitutive androstane receptor, in mouse liver.
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Transcription coactivator PRIP, the peroxisome proliferator-activated receptor (PPAR)-interacting protein, is redundant for the function of nuclear receptors PParalpha and CAR, the constitutive androstane receptor, in mouse liver.

机译：转录共激活因子PRIP（过氧化物酶体增殖物激活受体（PPAR）相互作用蛋白）对于小鼠肝脏中核受体PParalpha和CAR（组成型雄烷受体）的功能是多余的。

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摘要

Disruption of the genes encoding for the transcription coactivators, peroxisome proliferator-activated receptor (PPAR)-interacting protein (PRIP/ASC-2/RAP250/TRBP/NRC) and PPAR-binding protein (PBP/TRAP220/DRIP205/MED1), results in embryonic lethality by affecting placental and multiorgan development. Targeted deletion of coactivator PBP gene in liver parenchymal cells (PBP(LIV-/-)) results in the near abrogation of the induction of PPARalpha and CAR (constitutive androstane receptor)-regulated genes in liver. Here, we show that targeted deletion of coactivator PRIP gene in liver (PRIP(LIV-/-)) does not affect the induction of PPARalpha-regulated pleiotropic responses, including hepatomegaly, hepatic peroxisome proliferation, and induction of mRNAs of genes involved in fatty acid oxidation system, indicating that PRIP is not essential for PPARalpha-mediated transcriptional activity. We also provide additional data to show that liver-specific deletion of PRIP gene does not interfere with the induction of genes regulated by nuclear receptor CAR. Furthermore, disruption of PRIP gene in liver did not alter zoxazolamine-induced paralysis, and acetaminophen-induced hepatotoxicity. Studies with adenovirally driven EGFP-CAR expression in liver demonstrated that, unlike PBP, the absence of PRIP does not prevent phenobarbital-mediated nuclear translocation/retention of the receptor CAR in liver in vivo and cultured hepatocytes in vitro. These results show that PRIP deficiency in liver does not interfere with the function of nuclear receptors PPARalpha and CAR. The dependence of PPARalpha- and CAR-regulated gene transcription on coactivator PBP but not on PRIP attests to the existence of coactivator selectivity in nuclear receptor function.
机译：结果破坏了编码转录共激活因子，过氧化物酶体增殖物激活受体（PPAR）相互作用蛋白（PRIP / ASC-2 / RAP250 / TRBP / NRC）和PPAR结合蛋白（PBP / TRAP220 / DRIP205 / MED1）的基因通过影响胎盘和多器官发育来降低胚胎致死率。肝实质细胞（PBP（LIV-/-））中共激活因子PBP基因的靶向缺失导致肝脏中PPARalpha和CAR（组成性雄烷受体）调节基因的诱导几乎被废除。在这里，我们表明在肝脏中有针对性地删除共激活蛋白PRIP基因（PRIP（LIV-/-））不会影响PPARalpha调节的多效反应的诱导，包括肝肿大，肝过氧化物酶体增殖以及与脂肪相关基因的mRNA诱导酸氧化系统，表明PRIP对于PPARalpha介导的转录活性不是必需的。我们还提供其他数据，以显示PRIP基因的肝脏特异性缺失不会干扰由核受体CAR调控的基因的诱导。此外，肝脏中PRIP基因的破坏并没有改变唑唑胺引起的麻痹和对乙酰氨基酚引起的肝毒性。肝中由腺病毒驱动的EGFP-CAR表达的研究表明，与PBP不同，在体内和体外培养的肝细胞中，缺少PRIP并不能阻止苯巴比妥介导的受体CAR在细胞内的核转运/保留。这些结果表明，肝脏PRIP缺乏症不会干扰核受体PPARalpha和CAR的功能。 PPARalpha和CAR调节的基因转录对共激活因子PBP的依赖性，而不是对PRIP的依赖，证明了在核受体功能中共激活因子选择性的存在。

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