TY - JOUR
T1 - Understanding the Oxygen-Sensing Pathway and Its Therapeutic Implications in Diseases
AU - Liao, Chengheng
AU - Zhang, Qing
N1 - Funding Information:
Supported by the National Cancer Institute grants R01CA211732 and R21CA223675 , American Cancer Society Research Scholar Award TBE-132187 , Department of Defense Kidney Cancer Research Program grant W81XWH1910813 , and Cancer Prevention and Research Institute of Texas (CPRIT) grant RR190058 (Q.Z.).
Publisher Copyright:
© 2020 American Society for Investigative Pathology
PY - 2020/8
Y1 - 2020/8
N2 - Maintaining oxygen homeostasis is a most basic cellular process for adapting physiological oxygen variations, and its abnormality typically leads to various disorders in the human body. The key molecules of the oxygen-sensing system include the transcriptional regulator hypoxia-inducible factor (HIF), which controls a wide range of oxygen responsive target genes (eg, EPO and VEGF), certain members of the oxygen/2-oxoglutarate–dependent dioxygenase family, including the HIF proline hydroxylase (PHD, alias EGLN), and an E3 ubiquitin ligase component for HIF destruction called von Hippel–Lindau. In this review, we summarize the physiological role and highlight the pathologic function for each protein of the oxygen-sensing system. A better understanding of their molecular mechanisms of action will help uncover novel therapeutic targets and develop more effective treatment approaches for related human diseases, including cancer.
AB - Maintaining oxygen homeostasis is a most basic cellular process for adapting physiological oxygen variations, and its abnormality typically leads to various disorders in the human body. The key molecules of the oxygen-sensing system include the transcriptional regulator hypoxia-inducible factor (HIF), which controls a wide range of oxygen responsive target genes (eg, EPO and VEGF), certain members of the oxygen/2-oxoglutarate–dependent dioxygenase family, including the HIF proline hydroxylase (PHD, alias EGLN), and an E3 ubiquitin ligase component for HIF destruction called von Hippel–Lindau. In this review, we summarize the physiological role and highlight the pathologic function for each protein of the oxygen-sensing system. A better understanding of their molecular mechanisms of action will help uncover novel therapeutic targets and develop more effective treatment approaches for related human diseases, including cancer.
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U2 - 10.1016/j.ajpath.2020.04.003
DO - 10.1016/j.ajpath.2020.04.003
M3 - Review article
C2 - 32339495
AN - SCOPUS:85087021522
SN - 0002-9440
VL - 190
SP - 1584
EP - 1595
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 8
ER -