Nebert Daniel W
University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267-0056, USA.
Prog Lipid Res. 2017 Jul;67:38-57. doi: 10.1016/j.plipres.2017.06.001. Epub 2017 Jun 9.
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.
碱性螺旋-环-螺旋/芳香烃受体核转运蛋白-单胺氧化酶(bHLH/PAS)家族包含许多转录因子,存在于生物的所有三个界中;bHLH/PAS家族成员“感知”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、氧化还原电位、光子(光)、重力、热和渗透压。这些信号随后启动参与响应该信号的下游信号通路。术语“PAS”是“芳香烃受体核转运蛋白-单胺氧化酶”(per-Arnt-sim)的缩写,于1991年首次提出。尽管小鼠Arnt基因直到一九九一年才被鉴定出来,但其共转录结合伴侣芳烃受体(AHR)的证据早在1974年就作为外来化学物质的“传感器”被首次报道,它上调细胞色素P450家族1(CYP1)和其他通常代谢信号化学物质的酶活性。几年内,AHR也被认为参与炎症反应。小鼠的[Ah]位点在1973年至1989年期间被证明与化学致癌作用、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(-/-)基因敲除小鼠品系于1995年被报道。从20世纪70年代初到现在经过数千项研究,我们现在认识到AHR参与了数十个与关键生命过程有关的信号通路,几乎影响动物体内的每个器官和细胞类型,包括许多无脊椎动物。