Chemistry Research Laboratory and the Oxford Centre for Integrative Systems Biology, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
EMBO Rep. 2011 Jan;12(1):63-70. doi: 10.1038/embor.2010.170. Epub 2010 Nov 26.
The hypoxic response in humans is mediated by the hypoxia-inducible transcription factor (HIF), for which prolyl hydroxylases (PHDs) act as oxygen-sensing components. The evolutionary origins of the HIF system have been previously unclear. We demonstrate a functional HIF system in the simplest animal, Trichoplax adhaerens: HIF targets in T. adhaerens include glycolytic and metabolic enzymes, suggesting a role for HIF in the adaptation of basal multicellular animals to fluctuating oxygen levels. Characterization of the T. adhaerens PHDs and cross-species complementation assays reveal a conserved oxygen-sensing mechanism. Cross-genomic analyses rationalize the relative importance of HIF system components, and imply that the HIF system is likely to be present in all animals, but is unique to this kingdom.
在人类中，缺氧反应是由缺氧诱导转录因子 (HIF) 介导的，脯氨酰羟化酶 (PHD) 作为氧感应元件起作用。HIF 系统的进化起源以前尚不清楚。我们在最简单的动物 Trichoplax adhaerens 中证明了一个功能性的 HIF 系统：在 T. adhaerens 中，HIF 的靶标包括糖酵解和代谢酶，这表明 HIF 在基础多细胞动物适应波动的氧气水平方面发挥作用。对 T. adhaerens PHD 的特性和跨物种互补测定表明存在保守的氧感应机制。跨基因组分析合理化了 HIF 系统成分的相对重要性，并暗示 HIF 系统可能存在于所有动物中，但仅限于这个界。
