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缺氧诱导因子1(HIF-1)在缺氧诱导的哺乳动物细胞中广泛表达,为缺氧应答的全局性调控因子。HIF-1由HIF-1α和HIF-1β两种亚基组成,为异源二聚体转录因子。HIF-1α、HIF-1β和近年来发现的HIF-2α一样均属于bHLH转录因子超家族中的PAS亚族。HIF-1α的bHLH和PAS结构域与二聚化及DNA结合活性有关,TAD结构域则主要参与转录激活。HIF-1α的全长基因已克隆并在人和小鼠中定位。通过作用于靶基因的缺氧反应元件(HRE),HIF-1参与缺氧诱导的一系列基因的表达调控。HIF-1在生物体的氧气供应、细胞代谢、心血管发育以及一系列疾病生理病理中起重要作用,其活性调节存在多种层次。HIF-1/HRE基因选择表达系统已被应用于基因治疗中。
Hypoxia inducible factor 1 (HIF-1) is widely expressed in hypoxia-induced mammalian cells and is a global regulator of hypoxic response. HIF-1 is composed of two subunits, HIF-1α and HIF-1β, which are heterodimeric transcription factors. HIF-1α and HIF-1β belong to the PAS subfamily of bHLH transcription factor superfamily, as well as HIF-2α found in recent years. The bHLH and PAS domains of HIF-1α are associated with dimerization and DNA-binding activity, while the TAD domain is mainly involved in transcriptional activation. The full-length HIF-1α gene has been cloned and localized in humans and mice. Through hypoxia response element (HRE) acting on target gene, HIF-1 is involved in the regulation of hypoxia-induced expression of a series of genes. HIF-1 plays an important role in the organism’s oxygen supply, cell metabolism, cardiovascular development and a series of diseases and pathophysiological pathology, and there are many levels of its activity regulation. The HIF-1 / HRE gene selection expression system has been used in gene therapy.