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A more recent version of this article appeared on May 1, 2008
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Submitted on November 12, 2007
Revised on February 12, 2008
Accepted on March 3, 2008
*Turku Centre for Biotechnology, Turku University and Åbo Akademi University, FIN-29521 Turku, Finland; Institute of Physiology, University of Luebeck, D-23538 Luebeck, Germany; Department of Oncology and Radiation Therapy, Turku University Hospital, FIN-20520 Turku, Finland
Monitoring Editor: Jonathan Weissman
The HIF prolyl hydroxylases (PHDs/EGLNs) are central regulators of the molecular responses to oxygen availability. One isoform, PHD3, is expressed in response to hypoxia and causes apoptosis in oxygenated conditions in neural cells. Here we show that PHD3 forms subcellular aggregates in an oxygen-dependent manner. The aggregation of PHD3 was seen under normoxia and was strongly reduced under hypoxia or by the inactivation of the PHD3 hydroxylase activity. The PHD3 aggregates were dependent on microtubular integrity and contained components of the 26S proteasome, chaperones and ubiquitin thus demonstrating features that are characteristic for aggresome-like structures. Forced expression of the active PHD3 induced the aggregation of proteasomal components and activated apoptosis under normoxia in HeLa cells. The apoptosis was seen in cells prone to PHD3 aggregation and the PHD3 aggregation preceded apoptosis. The data demonstrates the cellular oxygen sensor PHD3 as a regulator of protein aggregation in response to varying oxygen availability.
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