Regulation of transcription and translation by hypoxia.
The maintenance of oxygen (O2) homeostasis is critical for embryonic development and postnatal life. In response to hypoxia, higher eukaryotes have developed coordinated mechanisms at both the transcriptional and translational levels to cope with this stress. Transcription of genes controlling glycolysis, glucose transport, cell survival and death, angiogenesis and erythropoiesis are activated (primarily by the hypoxia-inducible factor [HIF]) to facilitate cell survival and restore O2 homeostasis. During hypoxia, global protein synthesis is reduced to conserve ATP, while translation of factors like HIF-1alpha and VEGF that are critical for the hypoxic response is maintained by initiation via an internal ribosomal entry mechanism. This review addresses the regulatory effects of hypoxia on mRNA transcription and translation. As hypoxia is induced by tumor growth and affects tumor progression and metastasis, unraveling the basis of hypoxic control of transcription and translation will provide a better understanding of cancer physiology and development of anti-tumor therapies.
Liu
Liping
L
Howard Hughes Medical Institute, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Simon
M Celeste
MC
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen / Q000378:metabolism; D014176:Protein Biosynthesis; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen