Back to Browse Journals » Hypoxia » Volume 1

Prolyl-hydroxylase 3: evolving roles for an ancient signaling protein

Authors Place TL, Domann FE

Published Date October 2013 Volume 2013:1 Pages 13—27

DOI http://dx.doi.org/10.2147/HP.S50091

Received 18 June 2013, Accepted 1 August 2013, Published 16 October 2013

Trenton L Place,1 Frederick E Domann1,2

1Molecular and Cellular Biology Program, the University of Iowa, Iowa City, IA, USA; 2Department of Radiation Oncology, the University of Iowa, Iowa City, IA, USA

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 PHD 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 the complex nature of PHD3 expression and function in mammalian cells.

Keywords: PHD3, EGLN3, HIF–PHD, hypoxia-inducible factor, hypoxia, oxygen sensing

Download Article [PDF] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Readers of this article also read:

Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers

Nagelschmitz J, Blunck M, Kraetzschmar J, Ludwig M, Wensing G, Hohlfeld T

Clinical Pharmacology: Advances and Applications 2014, 6:51-59

Published Date: 19 March 2014

Population pharmacokinetics of olprinone in healthy male volunteers

Kunisawa T, Kasai H, Suda M, Yoshimura M, Sugawara A, Izumi Y, Iida T, Kurosawa A, Iwasaki H

Clinical Pharmacology: Advances and Applications 2014, 6:43-50

Published Date: 4 March 2014

Detemir as a once-daily basal insulin in type 2 diabetes

Nelson SE

Clinical Pharmacology: Advances and Applications 2011, 3:27-37

Published Date: 18 August 2011