Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. STKE, 18 October 2005
Vol. 2005, Issue 306, p. re12
[DOI: 10.1126/stke.3062005re12]

REVIEWS

Integration of Oxygen Signaling at the Consensus HRE

Roland H. Wenger*, Daniel P. Stiehl, and Gieri Camenisch

Institute of Physiology and Center for Integrative Human Physiology (CIHP), University of Zürich, CH-8057 Zürich, Switzerland.

Gloss: Oxygen availability regulates many physiological and pathophysiological processes, including embryonic development, high-altitude adaptation, wound healing, and inflammation, as well as contributing to the pathophysiology of ischemic diseases and cancer. Central to our understanding of these processes is an elucidation of the molecular mechanisms by which cells react and adapt to insufficient oxygen supply (hypoxia). The last few years have brought a wealth of novel insights into these processes. Oxygen-sensing protein hydroxylases have been discovered that regulate the abundance and activity of three hypoxia-inducible transcription factors (HIFs) and thereby the activity of at least 70 effector genes involved in hypoxic adaptation. In addition to the increase in HIF abundance in response to a decrease in tissue oxygenation, it became evident that HIF abundance is also proactively increased, even under normoxic conditions, in response to stimuli that lead to cell growth and thus ultimately require higher oxygen consumption. The growing cell thus profits from an anticipatory increase in HIF-dependent target gene expression. Growth stimuli–activated signaling pathways that influence the abundance and activity of HIFs include pathways that involve the activation of kinases and liberation of reactive oxygen species. All of these pathways converge at the hypoxia-response elements (HREs) of effector genes, to which the HIFs bind, thereby enabling HIF-dependent induction of gene expression.

*Corresponding author. Institute of Physiology and Center for Integrative Human Physiology (CIHP), University of Zürich-Irchel, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. E-Mail: roland.wenger{at}access.unizh.ch

Citation: R. H. Wenger, D. P. Stiehl, G. Camenisch, Integration of Oxygen Signaling at the Consensus HRE. Sci. STKE 2005, re12 (2005).

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
TSC2 Deficiency Increases PTEN via HIF1{alpha}.
L. Mahimainathan, N. Ghosh-Choudhury, B. Venkatesan, F. Das, C. C. Mandal, N. Dey, S. L. Habib, B. S. Kasinath, H. E. Abboud, and G. Ghosh Choudhury (2009)
J. Biol. Chem. 284, 27790-27798
   Abstract »    Full Text »    PDF »
Activation of hypoxia-inducible factor attenuates renal injury in rat remnant kidney.
Y. R. Song, S. J. You, Y.-M. Lee, H. J. Chin, D.-W. Chae, Y. K. Oh, K. W. Joo, J. S. Han, and K. Y. Na (2009)
Nephrol. Dial. Transplant.
   Abstract »    Full Text »    PDF »
Activation of a prometastatic gene expression program in hypoxic neuroblastoma cells.
P. Poomthavorn, S. H X Wong, S. Higgins, G. A Werther, and V. C Russo (2009)
Endocr. Relat. Cancer 16, 991-1004
   Abstract »    Full Text »    PDF »
HIF in Kidney Disease and Development.
L. Gunaratnam and J. V. Bonventre (2009)
J. Am. Soc. Nephrol. 20, 1877-1887
   Abstract »    Full Text »    PDF »
Hypoxia-inducible Factor Prolyl-4-hydroxylase PHD2 Protein Abundance Depends on Integral Membrane Anchoring of FKBP38.
S. Barth, F. Edlich, U. Berchner-Pfannschmidt, S. Gneuss, G. Jahreis, P. A. Hasgall, J. Fandrey, R. H. Wenger, and G. Camenisch (2009)
J. Biol. Chem. 284, 23046-23058
   Abstract »    Full Text »    PDF »
An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia.
Y. Benita, H. Kikuchi, A. D. Smith, M. Q. Zhang, D. C. Chung, and R. J. Xavier (2009)
Nucleic Acids Res. 37, 4587-4602
   Abstract »    Full Text »    PDF »
Genome-wide Association of Hypoxia-inducible Factor (HIF)-1{alpha} and HIF-2{alpha} DNA Binding with Expression Profiling of Hypoxia-inducible Transcripts.
D. R. Mole, C. Blancher, R. R. Copley, P. J. Pollard, J. M. Gleadle, J. Ragoussis, and P. J. Ratcliffe (2009)
J. Biol. Chem. 284, 16767-16775
   Abstract »    Full Text »    PDF »
Loss of VHL and Hypoxia Provokes PAX2 Up-Regulation in Clear Cell Renal Cell Carcinoma.
V.-D. Luu, G. Boysen, K. Struckmann, S. Casagrande, A. von Teichman, P. J. Wild, T. Sulser, P. Schraml, and H. Moch (2009)
Clin. Cancer Res. 15, 3297-3304
   Abstract »    Full Text »    PDF »
HIF at a glance.
M. C. Brahimi-Horn and J. Pouyssegur (2009)
J. Cell Sci. 122, 1055-1057
   Full Text »    PDF »
The Ubiquitin Ligase Siah2 and the Hypoxia Response.
K. Nakayama, J. Qi, and Z. Ronai (2009)
Mol. Cancer Res. 7, 443-451
   Abstract »    Full Text »    PDF »
Heterozygosity for Hypoxia Inducible Factor 1{alpha} Decreases the Incidence of Thymic Lymphomas in a p53 Mutant Mouse Model.
J. A. Bertout, S. A. Patel, B. H. Fryer, A. C. Durham, K. L. Covello, K. P. Olive, M. H. Goldschmidt, and M. C. Simon (2009)
Cancer Res. 69, 3213-3220
   Abstract »    Full Text »    PDF »
Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis.
X. Xia, M. E. Lemieux, W. Li, J. S. Carroll, M. Brown, X. S. Liu, and A. L. Kung (2009)
PNAS 106, 4260-4265
   Abstract »    Full Text »    PDF »
The Cooperative Induction of Hypoxia-Inducible Factor-1{alpha} and STAT3 during Hypoxia Induced an Impairment of Tumor Susceptibility to CTL-Mediated Cell Lysis.
M. Z. Noman, S. Buart, J. Van Pelt, C. Richon, M. Hasmim, N. Leleu, W. M. Suchorska, A. Jalil, Y. Lecluse, F. El Hage, et al. (2009)
J. Immunol. 182, 3510-3521
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 13 January 2009.
J. D. Scott, W. Wong, and A. M. VanHook (2009)
Science Signaling 2, pc1
   Abstract »    Full Text »
Human dendritic cells differentiated in hypoxia down-modulate antigen uptake and change their chemokine expression profile.
A. R. Elia, P. Cappello, M. Puppo, T. Fraone, C. Vanni, A. Eva, T. Musso, F. Novelli, L. Varesio, and M. Giovarelli (2008)
J. Leukoc. Biol. 84, 1472-1482
   Abstract »    Full Text »    PDF »
Impaired DNA double-strand break repair contributes to chemoresistance in HIF-1{alpha}-deficient mouse embryonic fibroblasts.
R. Wirthner, S. Wrann, K. Balamurugan, R. H. Wenger, and D. P. Stiehl (2008)
Carcinogenesis 29, 2306-2316
   Abstract »    Full Text »    PDF »
Essential Role of Developmentally Activated Hypoxia-Inducible Factor 1{alpha} for Cardiac Morphogenesis and Function.
J. Krishnan, P. Ahuja, S. Bodenmann, D. Knapik, E. Perriard, W. Krek, and J.-C. Perriard (2008)
Circ. Res. 103, 1139-1146
   Abstract »    Full Text »    PDF »
The HIF-1{alpha}-C/EBP{alpha} Axis.
H. P. Janardhan (2008)
Science Signaling 1, jc2
   Abstract »    Full Text »    PDF »
Transcriptional Regulation of Serine/Threonine Kinase-15 (STK15) Expression by Hypoxia and HIF-1.
A. Klein, D. Flugel, and T. Kietzmann (2008)
Mol. Biol. Cell 19, 3667-3675
   Abstract »    Full Text »    PDF »
Imaging of the hypoxia-inducible factor pathway: insights into oxygen sensing.
U. Berchner-Pfannschmidt, S. Frede, C. Wotzlaw, and J. Fandrey (2008)
Eur. Respir. J. 32, 210-217
   Abstract »    Full Text »    PDF »
Topotecan inhibits vascular endothelial growth factor production and angiogenic activity induced by hypoxia in human neuroblastoma by targeting hypoxia-inducible factor-1{alpha} and -2{alpha}.
M. Puppo, F. Battaglia, C. Ottaviano, S. Delfino, D. Ribatti, L. Varesio, and M. C. Bosco (2008)
Mol. Cancer Ther. 7, 1974-1984
   Abstract »    Full Text »    PDF »
Hypoxia-mediated Na-K-ATPase degradation requires von Hippel Lindau protein.
G. Zhou, L. A. Dada, N. S. Chandel, K. Iwai, E. Lecuona, A. Ciechanover, and J. I. Sznajder (2008)
FASEB J 22, 1335-1342
   Abstract »    Full Text »    PDF »
Hypoxia transcriptionally induces macrophage-inflammatory protein-3{alpha}/CCL-20 in primary human mononuclear phagocytes through nuclear factor (NF)-{kappa}B.
F. Battaglia, S. Delfino, E. Merello, M. Puppo, R. Piva, L. Varesio, and M. C. Bosco (2008)
J. Leukoc. Biol. 83, 648-662
   Abstract »    Full Text »    PDF »
Transcriptome of Hypoxic Immature Dendritic Cells: Modulation of Chemokine/Receptor Expression.
A. Ricciardi, A. R. Elia, P. Cappello, M. Puppo, C. Vanni, P. Fardin, A. Eva, D. Munroe, X. Wu, M. Giovarelli, et al. (2008)
Mol. Cancer Res. 6, 175-185
   Abstract »    Full Text »    PDF »
CCAAT/enhancer-binding protein {alpha} antagonizes transcriptional activity of hypoxia-inducible factor 1 {alpha} with direct protein-protein interaction.
L. Yang, Y. Jiang, S.F. Wu, M.Y. Zhou, Y.L. Wu, and G.Q. Chen (2008)
Carcinogenesis 29, 291-298
   Abstract »    Full Text »    PDF »
Hypoxia Up-Regulates Hypoxia-Inducible Factor-1{alpha} Transcription by Involving Phosphatidylinositol 3-Kinase and Nuclear Factor {kappa}B in Pulmonary Artery Smooth Muscle Cells.
R. S. BelAiba, S. Bonello, C. Zahringer, S. Schmidt, J. Hess, T. Kietzmann, and A. Gorlach (2007)
Mol. Biol. Cell 18, 4691-4697
   Abstract »    Full Text »    PDF »
Oxygen-dependent ATF-4 stability is mediated by the PHD3 oxygen sensor.
J. Koditz, J. Nesper, M. Wottawa, D. P. Stiehl, G. Camenisch, C. Franke, J. Myllyharju, R. H. Wenger, and D. M. Katschinski (2007)
Blood 110, 3610-3617
   Abstract »    Full Text »    PDF »
From critters to cancers: bridging comparative and clinical research on oxygen sensing, HIF signaling, and adaptations towards hypoxia.
D. Hoogewijs, N. B. Terwilliger, K. A. Webster, J. A. Powell-Coffman, S. Tokishita, H. Yamagata, T. Hankeln, T. Burmester, K. T. Rytkonen, M. Nikinmaa, et al. (2007)
Integr. Comp. Biol. 47, 552-577
   Abstract »    Full Text »    PDF »
Myocardial hypoxia-inducible HIF-1{alpha}, VEGF, and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia.
R. M. Bateman, C. Tokunaga, T. Kareco, D. R. Dorscheid, and K. R. Walley (2007)
Am J Physiol Heart Circ Physiol 293, H448-H456
   Abstract »    Full Text »    PDF »
Hypoxia-inducible Factor-1 (HIF-1) Is a Transcriptional Activator of the TrkB Neurotrophin Receptor Gene.
L. K. Martens, K. M. Kirschner, C. Warnecke, and H. Scholz (2007)
J. Biol. Chem. 282, 14379-14388
   Abstract »    Full Text »    PDF »
Glycogen Synthase Kinase 3 Phosphorylates Hypoxia-Inducible Factor 1{alpha} and Mediates Its Destabilization in a VHL-Independent Manner.
D. Flugel, A. Gorlach, C. Michiels, and T. Kietzmann (2007)
Mol. Cell. Biol. 27, 3253-3265
   Abstract »    Full Text »    PDF »
Reactive Oxygen Species Activate the HIF-1{alpha} Promoter Via a Functional NF{kappa}B Site.
S. Bonello, C. Zahringer, R. S. BelAiba, T. Djordjevic, J. Hess, C. Michiels, T. Kietzmann, and A. Gorlach (2007)
Arterioscler Thromb Vasc Biol 27, 755-761
   Abstract »    Full Text »    PDF »
Glucose-Stimulated Insulin Production in Mice Deficient for the PAS Kinase PASKIN.
E. Borter, M. Niessen, R. Zuellig, G. A. Spinas, P. Spielmann, G. Camenisch, and R. H. Wenger (2007)
Diabetes 56, 113-117
   Abstract »    Full Text »    PDF »
Translational Control of Collagen Prolyl 4-Hydroxylase-{alpha}(I) Gene Expression under Hypoxia.
M. Fahling, R. Mrowka, A. Steege, G. Nebrich, A. Perlewitz, P. B. Persson, and B. J. Thiele (2006)
J. Biol. Chem. 281, 26089-26101
   Abstract »    Full Text »    PDF »
Hypoxia Modifies the Transcriptome of Primary Human Monocytes: Modulation of Novel Immune-Related Genes and Identification Of CC-Chemokine Ligand 20 as a New Hypoxia-Inducible Gene.
M. C. Bosco, M. Puppo, C. Santangelo, L. Anfosso, U. Pfeffer, P. Fardin, F. Battaglia, and L. Varesio (2006)
J. Immunol. 177, 1941-1955
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882