Prolyl-hydroxylase 3: Evolving Roles for an Ancient Signaling Protein.
Article Details
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Place TL, Domann FE
Prolyl-hydroxylase 3: Evolving Roles for an Ancient Signaling Protein.
Hypoxia (Auckl). 2013 Oct 1;2013(1):13-17. doi: 10.2147/HP.S50091.
- PubMed ID
- 24672806 [ View in PubMed]
- Abstract
The ability of cells to sense oxygen is a highly evolved process that facilitates adaptations to the local oxygen environment and is critical to energy homeostasis. In vertebrates, this process is largely controlled by three intracellular prolyl-4-hydroxylases (PHD 1-3). These related enzymes share the ability to hydroxylate the hypoxia-inducible transcription factor (HIF), and therefore control the transcription of genes involved in metabolism and vascular recruitment. However, it is becoming increasingly apparent that proline-4-hydroxylation controls much more than HIF signaling, with PHD3 emerging as an exceptionally unique and functionally diverse PHD isoform. In fact, PHD3-mediated hydroxylation has recently been purported to function in such diverse roles as sympathetic neuronal and muscle development, sepsis, glycolytic metabolism, and cell fate. PHD3 expression is also highly distinct from that of the other PHD enzymes, and varies considerably between different cell types and oxygen concentrations. This review will examine the evolution of oxygen sensing by the HIF-family of PHD enzymes, with a specific focus on complex nature of PHD3 expression and function in mammalian cells.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Succinic acid Prolyl 3-hydroxylase 1 Protein Humans UnknownProduct ofDetails Succinic acid Prolyl 3-hydroxylase 2 Protein Humans UnknownProduct ofDetails Succinic acid Prolyl 3-hydroxylase 3 Protein Humans UnknownProduct ofDetails