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Volumn 8, Issue 5, 1998, Pages 588-594

Hypoxia-inducible factor 1: Master regulator of O2 homeostasis

Author keywords

[No Author keywords available]

Indexed keywords

OXYGEN; TRANSCRIPTION FACTOR;

EID: 0032190614     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(98)80016-6     Document Type: Article
Times cited : (960)

References (62)
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    • of special interest. Mouse HIF-1α mRNA containing exon I.1 is expressed ubiquitously whereas exon I.2-containing mRNA manifests a more variable level of expression among different tissues. The functional activity of the alternative isoform encoded by exon I.1 has not been determined and does not appear to have any relevance for human biology.
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    • of outstanding interest. Transactivation functions of HiF-1α are shown to be regulated by hypoxia in a complex, cell-type-specific manner independent of the regulation of HIF-1α protein levels. Two minimal, independently-functioning TADs, spanning amino acids 531-575 and 786-826, are identified in the context of fusion proteins containing an amino-terminal GAL4 DNA-binding domain. The data suggest that hypoxia results in a derepression of TAD function.
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    • of outstanding interest. This study links an oncogene to the induction of HIF-1 expression, thus providing one mechanism for hypoxic adaptation of tumor cells. In addition, the ability of three hepatoma subclones to form tumors in nude mice is directly related to their HIF-1 expression levels.
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    • Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth
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    • Induction of vascular growth factor by hypoxia is modulated by a phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia-inducible factor 1 transcriptional element
    • of special interest. A signalling pathway involving H-RAS, PI3 kinase, and AKT kinase leading to increased VEGF expression under hypoxic conditions is demonstrated. Although mutations in the HIF-1-binding site eliminated H-RAS-induced VEGF promoter activity, the factor mediating transcriptional activation is not determined.
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