Abstract
The heterodimeric transcription factor HIF-1 (hypoxia-inducible factor-1) induces angiogenesis, a process that is aberrantly elevated in cancer. The HIF-1β subunit is constitutively expressed, but the levels of the HIF-1α subunit are robustly regulated, increasing under hypoxic conditions and decreasing in normoxia. These changes result from rapid alterations in the rates of HIF-1α production and degradation. While the regulation of HIF-1α degradation is understood in significant detail, much less is known about the regulation of HIF-1α biosynthesis. Here, we review recent evidence that HIF-1α 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-1α mRNA and influence its half-life and translation rate. HIF-1α mRNA-binding factors are emerging as promising pharmacological targets to control HIF-1α production selectively and efficiently.
Keywords: Post-transcriptional gene regulation, RNA-binding proteins, microRNA, antisense RNA, IRES
Current Pharmaceutical Design
Title: Factors Interacting with HIF-1α mRNA: Novel Therapeutic Targets
Volume: 15 Issue: 33
Author(s): Stefanie Galban and Myriam Gorospe
Affiliation:
Keywords: Post-transcriptional gene regulation, RNA-binding proteins, microRNA, antisense RNA, IRES
Abstract: The heterodimeric transcription factor HIF-1 (hypoxia-inducible factor-1) induces angiogenesis, a process that is aberrantly elevated in cancer. The HIF-1β subunit is constitutively expressed, but the levels of the HIF-1α subunit are robustly regulated, increasing under hypoxic conditions and decreasing in normoxia. These changes result from rapid alterations in the rates of HIF-1α production and degradation. While the regulation of HIF-1α degradation is understood in significant detail, much less is known about the regulation of HIF-1α biosynthesis. Here, we review recent evidence that HIF-1α 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-1α mRNA and influence its half-life and translation rate. HIF-1α mRNA-binding factors are emerging as promising pharmacological targets to control HIF-1α production selectively and efficiently.
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Cite this article as:
Galban Stefanie and Gorospe Myriam, Factors Interacting with HIF-1α mRNA: Novel Therapeutic Targets, Current Pharmaceutical Design 2009; 15 (33) . https://dx.doi.org/10.2174/138161209789649376
DOI https://dx.doi.org/10.2174/138161209789649376 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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