Semenza G L
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3914, USA.
Annu Rev Cell Dev Biol. 1999;15:551-78. doi: 10.1146/annurev.cellbio.15.1.551.
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic-helix-loop-helix-PAS transcription factor consisting of HIF-1 alpha and HIF-1 beta subunits. HIF-1 alpha expression and HIF-1 transcriptional activity increase exponentially as cellular O2 concentration is decreased. Several dozen target genes that are transactivated by HIF-1 have been identified, including those encoding erythropoietin, glucose transporters, glycolytic enzymes, and vascular endothelial growth factor. The products of these genes either increase O2 delivery or allow metabolic adaptation to reduced O2 availability. HIF-1 is required for cardiac and vascular development and embryonic survival. In fetal and postnatal life, HIF-1 is required for a variety of physiological responses to chronic hypoxia. HIF-1 expression is increased in tumor cells by multiple mechanisms and may mediate adaptation to hypoxia that is critical for tumor progression. HIF-1 thus appears to function as a master regulator of O2 homeostasis that plays essential roles in cellular and systemic physiology, development, and pathophysiology.
缺氧诱导因子1（HIF-1）是一种异源二聚体碱性螺旋-环-螺旋-PAS转录因子，由HIF-1α和HIF-1β亚基组成。随着细胞氧浓度降低，HIF-1α表达和HIF-1转录活性呈指数增加。已鉴定出几十种由HIF-1反式激活的靶基因，包括那些编码促红细胞生成素、葡萄糖转运蛋白、糖酵解酶和血管内皮生长因子的基因。这些基因的产物要么增加氧输送，要么使代谢适应氧供应减少的情况。HIF-1是心脏和血管发育以及胚胎存活所必需的。在胎儿期和出生后，HIF-1是对慢性缺氧的多种生理反应所必需的。肿瘤细胞中HIF-1表达通过多种机制增加，并且可能介导对缺氧的适应，这对肿瘤进展至关重要。因此，HIF-1似乎作为氧稳态的主要调节因子，在细胞和全身生理、发育及病理生理中发挥重要作用。
