Kaelin William G, Ratcliffe Peter J
Howard Hughes Medical Institute, Boston, MA 02115, USA.
Mol Cell. 2008 May 23;30(4):393-402. doi: 10.1016/j.molcel.2008.04.009.
HIF plays a central role in the transcriptional response to changes in oxygen availability. The PHD family of oxygen-dependent prolyl hydroxylases plays a pivotal role in regulating HIF stability. The biochemical properties of these enzymes make them well suited to act as oxygen sensors. They also respond to other intracellular signals, including reactive oxygen species, nitric oxide, and certain metabolites, that can modulate the hypoxic response. HIF transcriptional activity is further tuned by FIH1-mediated asparagine hydroxylation. HIF affects signaling pathways that influence development, metabolism, inflammation, and integrative physiology. Accordingly, HIF-modulatory drugs are now being developed for diverse diseases.
缺氧诱导因子（HIF）在对氧可利用性变化的转录反应中起核心作用。氧依赖性脯氨酰羟化酶的脯氨酰羟化酶结构域（PHD）家族在调节HIF稳定性方面起关键作用。这些酶的生化特性使其非常适合作为氧传感器。它们还对其他细胞内信号作出反应，包括活性氧、一氧化氮和某些代谢物，这些信号可调节缺氧反应。HIF转录活性通过因子抑制HIF-1（FIH1）介导的天冬酰胺羟基化进一步调节。HIF影响影响发育、代谢、炎症和整合生理学的信号通路。因此，目前正在为多种疾病开发HIF调节药物。
