Abstract
The prolyl 4-hydroxylase domain protein 3 (PHD3) belongs to 2-oxoglutarate and iron-dependent dioxygenases. Together with the two closest paralogues, PHD1 and PHD2, these enzymes have been identified as cellular oxygen sensors that can mark the hypoxia-inducible factor α (HIF-α) for von Hippel-Lindau protein-mediated proteasomal destruction. Although having overlapping functions with PHD1 and PHD2, PHD3 markedly differs from the two isoforms. PHD3 shows a different expression pattern and subcellular localization as well as activity under low oxygen tension. Moreover, it has the widest range of non-HIF targets underlying its diverse functions. The functions of PHD3 differ depending on the cell type and also partially on the microenvironmental conditions it is expressed at. Under normoxia, PHD3 has been shown to be proapoptotic, but under hypoxia, it can have cell survival or proliferation-supporting functions. Here we discuss the regulation, targets, and functions of PHD3.
About the authors
Panu M. Jaakkola MD, PhD currently works as a medical oncologist at Turku University hospital. After getting his MD and PhD degrees at the University of Turku, Finland he did the post-doctoral period in Peter Ratcliffe’s laboratory at Oxford University. He currently runs a laboratory at the Turku Centre for Biotechnology at the University of Turku. The major focus of the laboratory is to understand how the oxygen sensing pathway and HIF prolyl hydroxylases affect carcinoma progression.
Krista Rantanen PhD is a geneticist who did her master’s thesis on lysinuric protein intolerance at the Department of Medical Genetics at the University of Turku, Finland. She did her PhD on the functions of PHD3 in Turku Centre for Biotechnology at the University of Turku and is currently a post-doctoral fellow at the Centre focusing on the renal cancer hypoxia and autophagy.
©2013 by Walter de Gruyter Berlin Boston
