Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 15, Issue 33, Pages 3853-3860Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138161209789649376
Keywords
Post-transcriptional gene regulation; RNA-binding proteins; microRNA; antisense RNA; IRES
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Funding
- National Institute on Aging
- National Institutes of Health
- [NIH T32 HL07517]
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The heterodimeric transcription factor HIF-1 (hypoxia-inducible factor-1) induces angiogenesis, a process that is aberrantly elevated in cancer. The HIF-1 beta subunit is constitutively expressed, but the levels of the HIF-1 alpha subunit are robustly regulated, increasing under hypoxic conditions and decreasing in normoxia. These changes result from rapid alterations in the rates of HIF-1 alpha production and degradation. While the regulation of HIF-1 alpha degradation is understood in significant detail, much less is known about the regulation of HIF-1 alpha biosynthesis. Here, we review recent evidence that HIF-1 alpha production is effectively controlled by post-transcriptional mechanisms. We focus on the RNA-binding proteins (RBPs) and the non-coding RNAs that interact with the HIF-1 alpha mRNA and influence its half-life and translation rate. HIF-1 alpha mRNA-binding factors are emerging as promising pharmacological targets to control HIF-1 alpha production selectively and efficiently.
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