HIF-1 信号转导通路 | Cell Signaling Technology
脯氨酸羟化可让它结合 von Hippel–Lindau 蛋白 (pVHL)，这是一种可靶向 HIF-α 进行蛋白酶体降解的 E3 泛素-连接酶。此外，在不缺氧的条件下，HIF-α 被抑制 HIF-1 (FIH) 的因子天冬酰胺酰羟基化，从而防止 HIF-α 结合共同激活蛋白 p300/CBP。
Biology of HIF-1α | Cell Death & Differentiation - Nature
2008年2月15日 · In the absence of hydroxylation due to hypoxia or PHD inhibition, HIF-1 α translocates to the nucleus, heterodimerizes with HIF-1 β and binds to hypoxia-response elements (HREs) in the...
缺氧和癌症：氧感应、代谢和肿瘤发生中的 HIF-1α
HIF-1 是一种异二聚体转录因子复合物，由两个亚基组成：应答 O 2 的 HIF-1α 亚基和结构性表达的 HIF-1β 亚基。 完整的 HIF-1 复合物与控制各种过程（例如代谢、增殖、凋亡和血管生成）的基因启动子中的缺氧反应元件 (HRE) 结合。 在正常O 2 水平（常氧）的情况下，HIF-1 靶基因被关闭。 从机制上讲，脯氨酰 4-羟化酶结构域蛋白 (PHD) 可以检测细胞中的氧含量，通过将（特定）脯氨酸残基上的 HIF-1α 亚基羟基化来应答氧的存在。 这促进了它与 von Hippel-Lindau 肿瘤抑 …
The purpose of the HIF-1/PHD feedback loop: to limit mTOR ... - PubMed
2011年5月15日 · We propose that the most relevant function of the PHD-HIF feedback loop is to limit the induction of HIF-1α by mTOR. The failure to limit mTOR-dependent induction of HIF-1 may contribute to age-related macular degeneration and diabetic retinopathy, suggesting rapamycin for prevention of these age-related diseases.
Role and regulation of prolyl hydroxylase domain proteins
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 degradation,...
缺氧信号通路 - 知乎 - 知乎专栏
HIF天冬酰胺羟化酶（Hypoxia-inducible factor 1-alpha inhibitor, HIF1AN）是通过羟化靶蛋白天冬酰胺残基修饰靶标蛋白功能的双加氧依赖性天冬酰胺酰羟化酶。 PHD和HIF1AN，在氧气受限的情况下，活性受到抑制，导致HIF-α快速聚集，并入核与HIF-1β发生异二聚化，在p300/CBP的共同作用下形成复合物，与基因启动子的缺氧应答元件（Hypoxia Response Element, HRE）的核心DNA序列5'-TACGTG-3'结合，激活下游基因的表达。
The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α …
2024年4月18日 · We investigated clinically used PHD inhibitors and a new selective PHD inhibitor (IOX5), to stabilize HIF-α in AML cells. PHD inhibition compromises AML in a HIF-1α-dependent manner to...
Inflammation and Hypoxia: HIF and PHD Isoform Selectivity
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 ...
HIF1α and metabolic reprogramming in inflammation - PMC
2016年10月3日 · In a resting cell, HIF1α is hydroxylated at conserved proline residues by the prolyl hydroxylases (PHDs). This hydroxylation allows for HIF1α ubiquitination by the von Hippel-Lindau (VHL) E3 ubiquitin ligase, marking it for rapid proteasomal degradation.
HIF-1α protects against oxidative stress by directly targeting ...
2019年1月14日 · The transcription factor hypoxia inducible factor-1α (HIF-1α) mediates adaptive responses to oxidative stress by nuclear translocation and regulation of gene expression. Mitochondrial changes are critical for the adaptive response to oxidative stress.
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