Factors interacting with HIF-1alpha mRNA: novel therapeutic targets.
The heterodimeric transcription factor HIF-1 (hypoxia-inducible factor-1) induces angiogenesis, a process that is aberrantly elevated in cancer. The HIF-1beta subunit is constitutively expressed, but the levels of the HIF-1alpha subunit are robustly regulated, increasing under hypoxic conditions and decreasing in normoxia. These changes result from rapid alterations in the rates of HIF-1alpha production and degradation. While the regulation of HIF-1alpha degradation is understood in significant detail, much less is known about the regulation of HIF-1alpha biosynthesis. Here, we review recent evidence that HIF-1alpha 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-1alpha mRNA and influence its half-life and translation rate. HIF-1alpha mRNA-binding factors are emerging as promising pharmacological targets to control HIF-1alpha production selectively and efficiently.
Galbán
Stefanie
S
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Gorospe
Myriam
M
D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation; D006207:Half-Life; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*
C497396:ARNT protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator