DDX5 enhances HIF-1 activity by promoting the interaction of HIF-1α with HIF-1β and recruiting the resulting heterodimer to its target gene loci

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Biology of the Cell Pub Date : 2023-11-30 DOI:10.1111/boc.202300077

Yukari Shirai, Tatsuya Suwa, Minoru Kobayashi, Sho Koyasu, Hiroshi Harada

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Abstract

Background Information

Cancer cells acquire malignant characteristics and therapy resistance by employing the hypoxia-inducible factor 1 (HIF-1)-dependent adaptive response to hypoxic microenvironment in solid tumors. Since the underlying molecular mechanisms remain unclear, difficulties are associated with establishing effective therapeutic strategies.

Results

We herein identified DEAD-box helicase 5 (DDX5) as a novel activator of HIF-1 and found that it enhanced the heterodimer formation of HIF-1α and HIF-1β and facilitated the recruitment of the resulting HIF-1 to its recognition sequence, hypoxia-response element (HRE), leading to the expression of a subset of cancer-related genes under hypoxia.

Conclusions

This study reveals that the regulation of HIF-1 recruitment to HRE is an important regulatory step in the control of HIF-1 activity.

Significance

The present study provides novel insights for the development of strategies to inhibit the HIF-1-dependent expression of cancer-related genes.

Abstract Image

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DDX5通过促进HIF-1α与HIF-1β的相互作用，并将产生的异源二聚体募集到其靶基因位点，从而增强HIF-1的活性。

在实体瘤中，癌细胞通过缺氧诱导因子1 (HIF-1)依赖性的适应性反应获得恶性特征和治疗耐药性。由于潜在的分子机制尚不清楚，因此建立有效的治疗策略存在困难。我们在此发现DEAD-box解旋酶5 (DDX5)是HIF-1的一种新的激活剂，发现它增强了HIF-1α和HIF-1β异源二聚体的形成，并促进了由此产生的HIF-1的募集到其识别方法:序列，缺氧反应元件(HRE)，导致缺氧下癌症相关基因亚群的表达。本研究揭示了HIF-1激活的分子机制，并为开发抑制HIF-1依赖性癌症相关基因表达的策略提供了新的见解。这篇文章受版权保护。版权所有。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biology of the Cell 生物-细胞生物学

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms. This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.