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Advances in Hypoxia-Inducible Factor Biology

机译：缺氧诱导因子生物学进展

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摘要

Hypoxia-inducible factor (HIF), a central regulator for detecting and adapting to cellular oxygen levels, transcriptionally activates genes modulating oxygen homeostasis and metabolic activation. Beyond this, HIF influences many other processes. Hypoxia, in part through HIF-dependent mechanisms, influences epigenetic factors, including DNA methylation and histone acetylation, which modulate hypoxia-responsive gene expression in cells. Hypoxia profoundly affects expression of many noncoding RNAs classes that have clinicopathological implications in cancer. HIF can regulate noncoding RNAs production, while, conversely, noncoding RNAs can modulate HIF expression. There is recent evidence for crosstalk between circadian rhythms and hypoxia-induced signaling, suggesting involvement of molecular clocks in adaptation to fluxes in nutrient and oxygen sensing. HIF induces increased production of cellular vesicles facilitating intercellular communication at a distance-for example, promoting angiogenesis in hypoxic tumors. Understanding the complex networks underlying cellular and genomic regulation in response to hypoxia via HIF may identify novel and specific therapeutic targets.
机译：缺氧诱导因子（HIF），用于检测和适应细胞氧水平的中央调节剂，转录激活调节氧气稳态和代谢活化的基因。除此之外，HIF会影响许多其他过程。部分通过HIF依赖性机制，影响表观遗传因素，包括DNA甲基化和组蛋白乙酰化，其调节细胞中的缺氧响应基因表达。缺氧深刻地影响许多非编码RNA类的表达，所述癌症在癌症中具有临床病理学意义。 HIF可以调节NOODING RNA生产，而相反地，非编码RNA可以调节HIF表达。最近在昼夜节律和缺氧诱导的信号之间进行串扰的证据，表明分子时钟在适应营养和氧气传感中的适应性。 HIF诱导促进在距离处的细胞间通信的细胞囊泡的产生增加 - 例如，在缺氧肿瘤中促进血管生成。理解依赖于Hy HIF的缺氧的蜂窝和基因组调节的复杂网络可以识别新颖和特异性治疗靶标。

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