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Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per-Arnt-sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals
Progress in Lipid Research ( IF 13.6 ) Pub Date : 2017-06-09 , DOI: 10.1016/j.plipres.2017.06.001
Daniel W. Nebert

The basic-helix/loop/helix per-Arnt-sim (bHLH/PAS) family comprises many transcription factors, found throughout all three kingdoms of life; bHLH/PAS members “sense” innumerable intracellular and extracellular “signals” — including endogenous compounds, foreign chemicals, gas molecules, redox potential, photons (light), gravity, heat, and osmotic pressure. These signals then initiate downstream signaling pathways involved in responding to that signal. The term “PAS”, abbreviation for “per-Arnt-sim” was first coined in 1991. Although the mouse Arnt gene was not identified until 1991, evidence of its co-transcriptional binding partner, aryl hydrocarbon receptor (AHR), was first reported in 1974 as a “sensor” of foreign chemicals, up-regulating cytochrome P450 family 1 (CYP1) and other enzyme activities that usually metabolize the signaling chemical. Within a few years, AHR was proposed also to participate in inflammation. The mouse [Ah] locus was shown (1973–1989) to be relevant to chemical carcinogenesis, mutagenesis, toxicity and teratogenesis, the mouse Ahr gene was cloned in 1992, and the first Ahr(−/−) knockout mouse line was reported in 1995. After thousands of studies from the early 1970s to present day, we now realize that AHR participates in dozens of signaling pathways involved in critical-life processes, affecting virtually every organ and cell-type in the animal, including many invertebrates.



中文翻译:

芳香烃受体(AHR):基本的螺旋/环的“先驱构件” /螺旋- ARNT - SIM(的bHLH / PAS)外国和内源性信号的“传感器”的家庭

每个Arnt-sim的基本螺旋/环/螺旋(bHLH / PAS)家族包含许多转录因子,遍及生命的三个王国。bHLH / PAS成员“感知”了无数的细胞内和细胞外“信号”,包括内源性化合物,外来化学物质,气体分子,氧化还原电势,光子(光),重力,热和渗透压。这些信号然后启动参与响应该信号的下游信号通路。对于术语“PAS”,简称“每ARNT-SIM ”于1991年首次创造虽然鼠标ARNT该基因直到1991年才被发现,其共转录结合伙伴芳烃受体(AHR)的证据首次于1974年被报道为外来化学物质的“传感器”,上调细胞色素P450家族1(CYP1)和其他酶通常会代谢信号化学物质的活性。几年之内,有人提出AHR也参与炎症。小鼠[ Ah ]基因座被证明(1973–1989)与化学致癌,诱变,毒性和致畸作用有关,小鼠Ahr基因于1992年被克隆,第一个Ahr基因被克隆。(-/-)基因敲除小鼠系于1995年报道。从1970年代初至今的数千项研究之后,我们现在意识到AHR参与了关键生命过程中涉及的数十种信号通路,几乎影响了每个器官和细胞,输入动物,包括许多无脊椎动物。

更新日期:2017-06-09
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