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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-20476

Wenger, R H; Camenisch, G; Stiehl, D P; Katschinski, D M (2009). HIF Prolyl-4-hydroxylase Interacting Proteins: Consequences for Drug Targeting. Current Pharmaceutical Design, 15(33):3886-3894.

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Abstract

Protein stability of hypoxia-inducible factor (HIF) alpha subunits is regulated by the oxygen-sensing prolyl-4-hydroxylase domain (PHD) enzymes. Under oxygen-limited conditions, HIF alpha subunits are stabilized and form active HIF transcription factors that induce a large number of genes involved in adaptation to hypoxic conditions with physiological implications for erythropoiesis, angiogenesis, cardiovascular function and cellular metabolism. Oxygen-sensing is regulated by the co-substrate-dependent activity and hypoxia-inducible abundance of the PHD enzymes which trigger HIF alpha stability even under low oxygen conditions. Because HIF alpha itself is notoriously reluctant to the development of
antagonists, an increase in PHD activity would offer an interesting alternative to the development of drugs that interfere specifically with the HIF signalling pathway. Interestingly, among the recently discovered PHD interacting proteins were not only novel downstream targets but also upstream regulators of PHDs. Their PHD isoform-specific interaction offers the possibility to target distinct PHD isoforms and their non-identical downstream signalling pathways. This review summarizes our current knowledge on PHD interacting proteins, including upstream regulators, chaperonins, scaffolding proteins, and novel downstream transcription factors.

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 October 2009
Deposited On:01 Sep 2009 07:35
Last Modified:27 Nov 2013 16:48
Publisher:Bentham Science
ISSN:1381-6128
Funders:Swiss National Science Foundation, Sassella Stiftung, Hartmann Müller-Stiftung, Olga Mayenfisch Stiftung, Krebsliga des Kantons Zürich, Deutsche Forschungsgemeinschaft, Wilhelm-Sander Stiftung
Publisher DOI:10.2174/138161209789649411
Official URL:http://www.benthamdirect.org/pages/content.php?CPD/2009/00000015/00000033/0008B.SGM
Related URLs:http://www.bentham.org/index.htm (Publisher)
PubMed ID:19671040
Citations:Web of Science®. Times Cited: 10
Google Scholar™
Scopus®. Citation Count: 13

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