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.
Abstract:
The hypoxia-inducible factor 1 (HIF-1) was initially identified as a transcription factor that regulated erythropoietin gene expression in response to a decrease in oxygen availability in kidney tissue. Subsequently, a family of oxygen-dependent protein hydroxylases was found to regulate the abundance and activity of three oxygen-sensitive HIF subunits, which, as part of the HIF heterodimer, regulated the transcription of at least 70 different effector genes. In addition to responding to a decrease in tissue oxygenation, HIF is proactively induced, even under normoxic conditions, in response to stimuli that lead to cell growth, ultimately leading to higher oxygen consumption. The growing cell thus profits from an anticipatory increase in HIF-dependent target gene expression. Growth stimuliactivated signaling pathways that influence the abundance and activity of HIFs include pathways in which kinases are activated and pathways in which reactive oxygen species are liberated. These pathways signal to the HIF protein hydroxylases, as well as to HIF itself, by means of covalent or redox modifications and protein-protein interactions. The final point of integration of all of these pathways is the hypoxia-response element (HRE) of effector genes. Here, we provide comprehensive compilations of the known growth stimuli that promote increases in HIF abundance, of protein-protein interactions involving HIF, and of the known HIF effector genes. The consensus HRE derived from a comparison of the HREs of these HIF effectors will be useful for identification of novel HIF target genes, design of oxygen-regulated gene therapy, and prediction of effects of future drugs targeting the HIF system.
*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. STKE2005, re12 (2005).
The editors suggest the following Related Resources on Science sites:
In Science Signaling
PODCASTS
John D. Scott, Wei Wong, and Annalisa M. VanHook (13 January 2009) Sci. Signal.2 (53), pc1.
[DOI: 10.1126/scisignal.253pc1] |Abstract »|Full Text »|Podcast »
PERSPECTIVES
Ian J. Frew and Wilhelm Krek (17 June 2008) Sci. Signal.1 (24), pe30.
[DOI: 10.1126/scisignal.124pe30] |Abstract »|Full Text »|PDF »
EDITORS' CHOICE
John F. Foley (27 March 2007) Sci. STKE2007 (379), tw99.
[DOI: 10.1126/stke.3792007tw99] |Abstract »
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.
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 »
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 »