Department of Pharmaceutical Sciences, School of Biomedical and Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (a Central University), Vidya Vihar Raibereli Road, Lucknow 226025 (U.P.), India.
Department of Pharmaceutical Sciences, Assam University, Silchar, Assam 788011, India.
Oxid Med Cell Longev. 2022 May 10;2022:2407223. doi: 10.1155/2022/2407223. eCollection 2022.
Hypoxia-inducible factor-1alpha (HIF-1) is a major transcription factor that adapts to low oxygen homeostasis and regulates the expression of several hypoxic genes, which aid in cancer survival and development. It has recently piqued the interest of translational researchers in the disciplines of cancer sciences. Hypoxia triggers an ample adaptive mechanism mediated via the HIF-1 transcriptional domain. Anaerobic glycolysis, angiogenesis, metastasis, and mitophagy are adaptive mechanisms that support tumor survival by promoting oxygen supply and regulating oxygen demand in hypoxic tumor cells. Throughout this pathway, the factor-inhibiting HIF-1 is a negative regulator of HIF-1 leading to its hydroxylation at the C-TAD domain of HIF-1 under normoxia. Thus, hydroxylated HIF-1 is unable to proceed with the transcriptional events due to interference in binding of C-TAD and CBP/p300. From this review, we can hypothesize that remodeling of FIH-1 activity is a unique mechanism that decreases the transcriptional activity of HIF-1 and, as a result, all of its hypoxic consequences. Hence, this review manuscript details the depth of knowledge of FIH-1 on hypoxia-associated cellular and molecular events, a potential strategy for targeting hypoxia-induced malignancies.
缺氧诱导因子-1α（HIF-1α）是一种主要的转录因子，适应低氧内稳态，并调节几种低氧基因的表达，这些基因有助于癌症的存活和发展。它最近引起了癌症科学领域的转化研究人员的兴趣。缺氧通过 HIF-1 转录结构域引发丰富的适应性机制。无氧糖酵解、血管生成、转移和线粒体自噬是适应性机制，通过促进缺氧肿瘤细胞的氧气供应和调节氧气需求来支持肿瘤存活。在整个途径中，因子抑制 HIF-1 是 HIF-1 的负调节剂，导致 HIF-1 在正常氧下在 HIF-1 的 C-TAD 结构域发生羟化。因此，由于 C-TAD 和 CBP/p300 结合的干扰，羟化的 HIF-1 无法进行转录事件。从这篇综述中，我们可以假设，FIH-1 活性的重塑是一种降低 HIF-1 转录活性的独特机制，因此，所有的低氧后果。因此，本综述详细介绍了 FIH-1 对缺氧相关细胞和分子事件的深度了解，这是针对缺氧诱导的恶性肿瘤的潜在策略。
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