低氧诱导因子(hypoxia-inducible factor, HIF)是体内参与细胞低氧应答的主要转录因子， 而氧依赖性的脯氨酸羟化酶(prolyl hydroxylase, PHD)是HIF降解反应的限速酶，可羟基化HIF的脯氨酸残基，使HIF被蛋白酶

2020年4月30日 · 活性低氧诱导因子脯氨酰羟化酶（hif-phd）抑制剂，已开发的适应证为肾性贫血。 全球首款HIF-PHD抑制剂获批上市。 HIF-PHD在HIF的降解中起关键作用。

2008年2月15日 · Oxygen-dependent hydroxylation of hypoxia-inducible factor (HIF)- α subunits by prolyl hydroxylase domain (PHD) proteins signals their polyubiquitination and proteasomal...

PHD发现了四种，即PHD1-3以及PHD-TM (PHD4)， 但PHD2在HIF-1α的分解中起主要作用。 因为依赖氧气，所以氧气不足——氧气浓度不断降低的时候，HIF-1α的泛素化就会减少，于是HIF-1α的分解就会减少，而合成速率不变或者通过某些继发的转录或者翻译调节途径而增加，因此HIF-1α的浓度迅速增加，从而到细胞核里去促进转录等等。 研究发现HIF-1α这个玩意还挺烈性的，赛门扎当初发现HIF-1α的时候，是把肝癌细胞放进1%的低氧环境中，结果发现促红细胞生成素 …

脯氨酸羟化酶(prolyl hydroxylase，PHD)是缺氧诱导因子(hypoxia inducible factor，HIF)通路的重要调节因子之一。 在氧气受限的情况下，PHD的活性受到抑制，通过各种机理调节细胞内的氧适应水平，包括mTOR通路、NF-κB通路、细胞凋亡和细胞代谢等， 从而参与多种疾病的发生 ...

The hypoxia-inducible factor (HIF)–prolyl hydroxylase domain (PHD) pathway regulates cellular responses to hypoxia and is involved in multiple diseases, including anemia, polycythemia, ischemic diseases, pulmonary arterial hypertension, and cancer. 10 HIF-PHD inhibitors (HIF-PHIs) are a new class of drugs that activate HIF transcription ...

2019年1月1日 · Cells sense and respond to hypoxia through the activity of the transcription factor HIF (hypoxia-inducible factor) and its regulatory hydroxylases, the prolyl hydroxylase domain enzymes (PHDs). Multiple isoforms of HIFs and PHDs exist, and isoform-selective roles have been identified in the context of the inflammatory environment, which is ...

2018年12月10日 · Hypoxia-inducible factors (HIFs) are key transcription heterodimers consisting of regulatory α-subunits (HIF-1α, HIF-2α, HIF-3α) and a constitutive β-subunit (HIF-β). Regulation of downstream targets determines the fate of NSCs.

HIF prolyl hydroxylase domain-2 (PHD2) has long been recognized as the major regulator of this response, controlling a myriad of outcomes that range from cell death to proliferation. However, this enzyme has been associated with more pathways, making the role of this protein remarkably complex under distinct pathologies.

In this review, I discuss the process of molecular cloning of HIF and HIF-PH, which explains hypoxia-induced EPO expression; the development of HIF-PH inhibitors that artificially or exogenously activate HIF by inhibiting HIF-PH; and the significance and implications of medical intervention using HIF-PH inhibitors.