Transcriptional Control of Hepatocanalicular Transporter Gene Expression

Transcriptional Control of Hepatocanalicular Transporter Gene Expression
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肝小管转运蛋白基因表达的转录控制

DOI:
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发表时间:
2000
期刊:
Seminars in liver disease (Print)
影响因子:
--
通讯作者:
Michael Müller
Michael Müller
中科院分区:
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文献类型:
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作者:
Michael Müller

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较大有机溶质在小管膜的转运过程主要由ATP结合盒(ABC)转运蛋白超家族成员驱动。这些转运蛋白的功能范围从胆汁成分分泌到异生物质和II相缀合物输出。它们各自基因表达的转录控制不同,这可能是为了保证组织特异性,对胁迫的有效反应或底物浓度的变化。在细胞核内,竞争和特异性激活的转录因子的浓度决定了转运蛋白基因表达中的转录激活。一些转录因子作为代谢物(LXR、FXR、CAR、SREBP、PPARs)、外源性物质(PPARs、PXR)、氧化应激(NF-κ B、AP-1)或DNA损伤(p53)的传感器。其核浓度和活性的变化将影响在其5 '-启动子/增强子DNA序列中含有特异性应答元件的相应靶基因的转录速率。到目前为止,对大多数ABC转运蛋白的转录控制知之甚少。然而,由于在分子生物学的巨大进步,许多工具已成为最近可用于研究和理解的“核内的战斗”方面的肝转运蛋白基因的表达。
Transport processes for larger organic solutes at the canalicular membrane are mainly driven by members of the superfamily of ATP-binding cassette (ABC) transporters. The functions of these transporters range from bile component secretion to xenobiotica and phase II-conjugate export. The transcriptional control of the expression of their respective genes differs, and this may be to guarantee tissue specificity, effective response to stress, or changes in substrate concentrations. Inside the nucleus, the concentration of competing and specifically activated transcription factors determines the transcriptional activation in transporter gene expression. Some transcription factors function as sensors for metabolites (LXR, FXR, CAR, SREBP, PPARs), xenobiotics (PPARs, PXR), oxidative stress (NF-kappa B, AP-1), or DNA damage (p53). Changes in their nuclear concentrations and activity will influence the transcription rates of the respective target genes that contain specific responsive elements in their 5'-promoter/enhancer DNA sequences. Until now little was known about the transcriptional control of most ABC transporter proteins. However, due to the enormous progress in molecular biology, many tools have become recently available to study and understand the "battle inside the nucleus" with respect to hepatic transporter gene expression.
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