Role of the aryl hydrocarbon receptor in cell cycle regulation
Role of the aryl hydrocarbon receptor in cell cycle regulation
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DOI：
10.1016/s0300-483x(02)00276-7
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发表时间：
2002-12-27
期刊：
影响因子：
4.5
通讯作者：
Knudsen, ES
中科院分区：
文献类型：
--
作者：
Puga, A;Marlowe, J;Knudsen, ES
多环芳烃化合物的生物学影响最令人困惑的方面之一是，它们在暴露的动物和人类中引起明显不相关的各种毒性、致畸性和致癌性反应。在细胞水平上，这些环境毒物影响细胞周期调节机制和信号转导途径的方式是同样不同的，往往是矛盾的。例如，根据所研究的特定细胞系，暴露于这些化合物可能导致细胞增殖、终末分化或凋亡。这些作用是由芳烃受体介导的，芳烃受体是一种配体激活的转录因子，以其对几个I期解毒细胞色素P450基因表达的调节活性而闻名。对芳香烃受体功能的分子机制的研究揭示了这种蛋白在细胞周期进程中的新作用。激活的受体作为环境传感器和细胞周期检查点，使暴露于不利环境刺激的细胞在DNA复制开始之前停止。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
One of the most puzzling aspects of the biological impact of polycyclic aromatic hydrocarbon compounds is that they elicit an apparently unrelated variety of toxic, teratogenic, and carcinogenic responses in exposed animals and in humans. At the cellular level, these environmental toxicants affect cell cycle regulatory mechanisms and signal transduction pathways in ways that are equally diverse and often contradictory. For example, depending on the particular cell lines studied, exposure to these compounds may lead to cell proliferation, to terminal differentiation, or to apoptosis. These effects are mediated by the aryl hydrocarbon receptor, a ligand-activated transcription factor well known for its regulatory activity on the expression of several phase I detoxification cytochrome P450 genes. Research into the molecular mechanisms of aryl hydrocarbon receptor function has uncovered a novel role for this protein during cell cycle progression. The activated receptor acts as an environmental sensor and cell cycle checkpoint that commits cells exposed to adverse environmental stimuli to arrest before the onset of DNA replication. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.