Affiliation:
1. Laboratory of Cancer Cell Biology Graduate School of Biostudies Kyoto University Kyoto Japan
2. Department of Genome Repair Dynamics Radiation Biology Center Graduate School of Biostudies Kyoto University Kyoto Japan
3. Medical Research Council Oxford Institute for Radiation Oncology Department of Oncology University of Oxford Oxford UK
4. Department of Diagnostic Imaging and Nuclear Medicine Graduate School of Medicine Kyoto University Kyoto Japan
Abstract
AbstractBackground InformationCancer 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.ResultsWe 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.ConclusionsThis study reveals that the regulation of HIF‐1 recruitment to HRE is an important regulatory step in the control of HIF‐1 activity.SignificanceThe present study provides novel insights for the development of strategies to inhibit the HIF‐1‐dependent expression of cancer‐related genes.
Funder
Daiichi Sankyo Foundation of Life Science
Suzuken Memorial Foundation
Japan Agency for Medical Research and Development
Princess Takamatsu Cancer Research Fund
Japan Society for the Promotion of Science
Takeda Science Foundation
Uehara Memorial Foundation
Kobayashi Foundation for Cancer Research
Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care
Foundation for Promotion of Cancer Research
Yasuda Memorial Medical Foundation
Subject
Cell Biology,General Medicine