化学
缺氧(环境)
转录因子
缺氧诱导因子1
细胞适应
信号转导
重编程
调节器
蛋白质亚单位
癌症
抄写(语言学)
癌细胞
HIF1A型
缺氧诱导因子
Sp3转录因子
细胞生物学
癌症研究
生物化学
细胞
基因
增强子
氧气
遗传学
生物
有机化学
语言学
哲学
作者
Andrew T. Ball,Soran Mohammed,Cyrielle Doigneaux,Reece M. Gardner,James W. Easton,Steve Turner,Jonathan W. Essex,Garry Pairaudeau,Ali Tavassoli
摘要
Hypoxia inducible factor (HIF) is a heterodimeric transcription factor composed of an oxygen-regulated α subunit and a constitutively expressed β subunit that serves as the master regulator of the cellular response to low oxygen concentrations. The HIF transcription factor senses and responds to hypoxia by significantly altering transcription and reprogramming cells to enable adaptation to a hypoxic microenvironment. Given the central role played by HIF in the survival and growth of tumors in hypoxia, inhibition of this transcription factor serves as a potential therapeutic approach for treating a variety of cancers. Here, we report the identification, optimization, and characterization of a series of cyclic peptides that disrupt the function of HIF-1 and HIF-2 transcription factors by inhibiting the interaction of both HIF-1α and HIF-2α with HIF-1β. These compounds are shown to bind to HIF-α and disrupt the protein-protein interaction between the α and β subunits of the transcription factor, resulting in disruption of hypoxia-response signaling by our lead molecule in several cancer cell lines.
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