Richard K. Bruick, Steven L. McKnight^*

Mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of HIF is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in HIF. We identified a conserved family of HIF prolyl hydoxylase (HPH) enzymes that appear to be responsible for this posttranslational modification. In cultured mammalian cells, inappropriate accumulation of HIF caused by forced expression of the HIF-1 subunit under normoxic conditions was attenuated by coexpression of HPH. Suppression of HPH in cultured Drosophila melanogaster cells by RNA interference resulted in elevated expression of a hypoxia-inducible gene (LDH, encoding lactate dehydrogenase) under normoxic conditions. These findings indicate that HPH is an essential component of the pathway through which cells sense oxygen.

Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard L3.124, Dallas, TX 75390-9152, USA.
^*   To whom correspondence should be addressed. E-mail: smckni{at}biochem.swmed.edu

DCNL1 Functions as a Substrate Sensor and Activator of Cullin 2-RING Ligase.

P. Heir, R. I. Sufan, S. N. Greer, B. P. Poon, J. E. Lee, and M. Ohh (2013)
Mol. Cell. Biol. 33, 1621-1631
 |  Abstract »  |  Full Text »  |  PDF »

Oxygen sensing and hypoxia signalling pathways in animals: the implications of physiology for cancer.

P. J. Ratcliffe (2013)
J. Physiol. 591, 2027-2042
 |  Abstract »  |  Full Text »  |  PDF »

Prolyl Hydroxylase Domain Protein 2 (PHD2) Binds a Pro-Xaa-Leu-Glu Motif, Linking It to the Heat Shock Protein 90 Pathway.

D. Song, L.-S. Li, K. J. Heaton-Johnson, P. R. Arsenault, S. R. Master, and F. S. Lee (2013)
J. Biol. Chem. 288, 9662-9674
 |  Abstract »  |  Full Text »  |  PDF »

Hypoxia-Response Element (HRE)-Directed Transcriptional Regulation of the Rat Lysyl Oxidase Gene in Response to Cobalt and Cadmium.

S. Gao, J. Zhou, Y. Zhao, P. Toselli, and W. Li (2013)
Toxicol. Sci. 132, 379-389
 |  Abstract »  |  Full Text »  |  PDF »

A dynamic model of the hypoxia-inducible factor 1{alpha} (HIF-1{alpha}) network.

L. K. Nguyen, M. A. S. Cavadas, C. C. Scholz, S. F. Fitzpatrick, U. Bruning, E. P. Cummins, M. M. Tambuwala, M. C. Manresa, B. N. Kholodenko, C. T. Taylor, et al. (2013)
J. Cell Sci. 126, 1454-1463
 |  Abstract »  |  Full Text »  |  PDF »

Selective Inhibition of Hypoxia-Inducible Factor 1{alpha} Ameliorates Adipose Tissue Dysfunction.

K. Sun, N. Halberg, M. Khan, U. J. Magalang, and P. E. Scherer (2013)
Mol. Cell. Biol. 33, 904-917
 |  Abstract »  |  Full Text »  |  PDF »

p62/SQSTM1 regulates cellular oxygen sensing by attenuating PHD3 activity through aggregate sequestration and enhanced degradation.

K. Rantanen, J.-P. Pursiheimo, H. Hogel, P. Miikkulainen, J. Sundstrom, and P. M. Jaakkola (2013)
J. Cell Sci. 126, 1144-1154
 |  Abstract »  |  Full Text »  |  PDF »

Identification of CDCP1 as a hypoxia-inducible factor 2{alpha} (HIF-2{alpha}) target gene that is associated with survival in clear cell renal cell carcinoma patients.

B. M. Emerling, C. H. Benes, G. Poulogiannis, E. L. Bell, K. Courtney, H. Liu, R. Choo-Wing, G. Bellinger, K. S. Tsukazawa, V. Brown, et al. (2013)
PNAS 110, 3483-3488
 |  Abstract »  |  Full Text »  |  PDF »

The Kaposi's Sarcoma-Associated Herpesvirus ORF34 Protein Binds to HIF-1{alpha} and Causes Its Degradation via the Proteasome Pathway.

M. Haque and K. G. Kousoulas (2013)
J. Virol. 87, 2164-2173
 |  Abstract »  |  Full Text »  |  PDF »

Dysregulation of Hypoxia-Inducible Factor by Presenilin/{gamma}-Secretase Loss-of-Function Mutations.

M. R. Kaufmann, S. Barth, U. Konietzko, B. Wu, S. Egger, R. Kunze, H. H. Marti, M. Hick, U. Muller, G. Camenisch, et al. (2013)
J. Neurosci. 33, 1915-1926
 |  Abstract »  |  Full Text »  |  PDF »

The Role of Hypoxia and Hypoxia-Inducible Factor-1Alpha in Preeclampsia Pathogenesis.

R. Tal (2012)
Biol Reprod 87, 134
 |  Abstract »  |  Full Text »  |  PDF »

Transmembrane prolyl 4-hydroxylase is a fourth prolyl 4-hydroxylase regulating EPO production and erythropoiesis.

A. Laitala, E. Aro, G. Walkinshaw, J. M. Maki, M. Rossi, M. Heikkila, E.-R. Savolainen, M. Arend, K. I. Kivirikko, P. Koivunen, et al. (2012)
Blood 120, 3336-3344
 |  Abstract »  |  Full Text »  |  PDF »

Impacts of Hypoxia-Inducible Factor-1 Knockout in the Retinal Pigment Epithelium on Choroidal Neovascularization.

M. Lin, Y. Hu, Y. Chen, K. K. Zhou, J. Jin, M. Zhu, Y.-Z. Le, J. Ge, and J.-x. Ma (2012)
Invest. Ophthalmol. Vis. Sci. 53, 6197-6206
 |  Abstract »  |  Full Text »  |  PDF »

The Acetylase/Deacetylase Couple CREB-binding Protein/Sirtuin 1 Controls Hypoxia-inducible Factor 2 Signaling.

R. Chen, M. Xu, R. T. Hogg, J. Li, B. Little, R. D. Gerard, and J. A. Garcia (2012)
J. Biol. Chem. 287, 30800-30811
 |  Abstract »  |  Full Text »  |  PDF »

The Prolyl Hydroxylase PHD3 Identifies Proinflammatory Macrophages and Its Expression Is Regulated by Activin A.

M. M. Escribese, E. Sierra-Filardi, C. Nieto, R. Samaniego, C. Sanchez-Torres, T. Matsuyama, E. Calderon-Gomez, M. A. Vega, A. Salas, P. Sanchez-Mateos, et al. (2012)
J. Immunol. 189, 1946-1954
 |  Abstract »  |  Full Text »  |  PDF »

Expression Profiling of Attenuated Mitochondrial Function Identifies Retrograde Signals in Drosophila.

W. A. Freije, S. Mandal, and U. Banerjee (2012)
g3 2, 843-851
 |  Abstract »  |  Full Text »  |  PDF »

The balance of beneficial and deleterious effects of hypoxia-inducible factor activation by prolyl hydroxylase inhibitor in rat remnant kidney depends on the timing of administration.

X. Yu, Y. Fang, H. Liu, J. Zhu, J. Zou, X. Xu, S. Jiang, and X. Ding (2012)
Nephrol. Dial. Transplant. 27, 3110-3119
 |  Abstract »  |  Full Text »  |  PDF »

MicroRNA-31 targets FIH-1 to positively regulate corneal epithelial glycogen metabolism.

H. Peng, R. B. Hamanaka, J. Katsnelson, L.-L. Hao, W. Yang, N. S. Chandel, and R. M. Lavker (2012)
FASEB J 26, 3140-3147
 |  Abstract »  |  Full Text »  |  PDF »

Adaptive and Maladaptive Cardiorespiratory Responses to Continuous and Intermittent Hypoxia Mediated by Hypoxia-Inducible Factors 1 and 2.

N. R. Prabhakar and G. L. Semenza (2012)
Physiol Rev 92, 967-1003
 |  Abstract »  |  Full Text »  |  PDF »

Coming into View: Eukaryotic Iron Chaperones and Intracellular Iron Delivery.

C. C. Philpott (2012)
J. Biol. Chem. 287, 13518-13523
 |  Abstract »  |  Full Text »  |  PDF »

The protective effect of prolyl-hydroxylase inhibition against renal ischaemia requires application prior to ischaemia but is superior to EPO treatment.

Z. Wang, G. Schley, G. Turkoglu, N. Burzlaff, K. U. Amann, C. Willam, K.-U. Eckardt, and W. M. Bernhardt (2012)
Nephrol. Dial. Transplant. 27, 929-936
 |  Abstract »  |  Full Text »  |  PDF »

The Ubiquitin-Proteasome System Meets Angiogenesis.

N. Rahimi (2012)
Mol. Cancer Ther. 11, 538-548
 |  Abstract »  |  Full Text »  |  PDF »

GSK-3{beta} regulates cell growth, migration, and angiogenesis via Fbw7 and USP28-dependent degradation of HIF-1{alpha}.

D. Flugel, A. Gorlach, and T. Kietzmann (2012)
Blood 119, 1292-1301
 |  Abstract »  |  Full Text »  |  PDF »

Green tea polyphenol EGCG suppresses lung cancer cell growth through upregulating miR-210 expression caused by stabilizing HIF-1{alpha}.

H. Wang, S. Bian, and C. S. Yang (2011)
Carcinogenesis 32, 1881-1889
 |  Abstract »  |  Full Text »  |  PDF »

Prolyl 4-hydroxylase genes are subjected to alternative splicing in roots of maize seedlings under waterlogging.

X. Zou, Y. Jiang, Y. Zheng, M. Zhang, and Z. Zhang (2011)
Ann. Bot. 108, 1323-1335
 |  Abstract »  |  Full Text »  |  PDF »

Hypoxia-induced transcriptional repression of the melanoma-associated oncogene MITF.

E. Feige, S. Yokoyama, C. Levy, M. Khaled, V. Igras, R. J. Lin, S. Lee, H. R. Widlund, S. R. Granter, A. L. Kung, et al. (2011)
PNAS 108, E924-E933
 |  Abstract »  |  Full Text »  |  PDF »

Cell-Autonomous and Non-Cell-Autonomous Neuroprotective Functions of ROR{alpha} in Neurons and Astrocytes during Hypoxia.

S. Jolly, N. Journiac, F. Naudet, V. Gautheron, J. Mariani, and B. Vernet-der Garabedian (2011)
J. Neurosci. 31, 14314-14323
 |  Abstract »  |  Full Text »  |  PDF »

MicroRNAs: New Players in Cardiac Injury and Protection.

R. C. Kukreja, C. Yin, and F. N. Salloum (2011)
Mol. Pharmacol. 80, 558-564
 |  Abstract »  |  Full Text »  |  PDF »

Hypoxia Inducible Factor-2{alpha} Is Translationally Repressed in Response to Dietary Iron Deficiency in Sprague-Dawley Rats.

M. R. Davis, K. M. Shawron, E. Rendina, S. K. Peterson, E. A. Lucas, B. J. Smith, and S. L. Clarke (2011)
J. Nutr. 141, 1590-1596
 |  Abstract »  |  Full Text »  |  PDF »

Hypoxic induction of vascular endothelial growth factor regulates murine hematopoietic stem cell function in the low-oxygenic niche.

M. Rehn, A. Olsson, K. Reckzeh, E. Diffner, P. Carmeliet, G. Landberg, and J. Cammenga (2011)
Blood 118, 1534-1543
 |  Abstract »  |  Full Text »  |  PDF »

Activation of hypoxia-inducible factor-1{alpha} (Hif-1{alpha}) delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model.

P. M. Elks, F. J. van Eeden, G. Dixon, X. Wang, C. C. Reyes-Aldasoro, P. W. Ingham, M. K. B. Whyte, S. R. Walmsley, and S. A. Renshaw (2011)
Blood 118, 712-722
 |  Abstract »  |  Full Text »  |  PDF »

HIF Takes It Up a Notch.

E. A. Johnson (2011)
Science Signaling 4, pe33
 |  Abstract »  |  Full Text »  |  PDF »

Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2{alpha} gain-of-function mutation.

F. Formenti, P. A. Beer, Q. P. P. Croft, K. L. Dorrington, D. P. Gale, T. R. J. Lappin, G. S. Lucas, E. R. Maher, P. H. Maxwell, M. F. McMullin, et al. (2011)
FASEB J 25, 2001-2011
 |  Abstract »  |  Full Text »  |  PDF »

Pharmacological Characterization of 1-(5-Chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic Acid (JNJ-42041935), a Potent and Selective Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor.

T. D. Barrett, H. L. Palomino, T. I. Brondstetter, K. C. Kanelakis, X. Wu, P. V. Haug, W. Yan, A. Young, H. Hua, J. C. Hart, et al. (2011)
Mol. Pharmacol. 79, 910-920
 |  Abstract »  |  Full Text »  |  PDF »

Ascorbic acid regulates osterix expression in osteoblasts by activation of prolyl hydroxylase and ubiquitination-mediated proteosomal degradation pathway.

W. Xing, S. Pourteymoor, and S. Mohan (2011)
Physiol Genomics 43, 749-757
 |  Abstract »  |  Full Text »  |  PDF »

Vitamin C is dispensable for oxygen sensing in vivo.

K. J. Nytko, N. Maeda, P. Schlafli, P. Spielmann, R. H. Wenger, and D. P. Stiehl (2011)
Blood 117, 5485-5493
 |  Abstract »  |  Full Text »  |  PDF »

Src activates HIF-1{alpha} not through direct phosphorylation of HIF-1{alpha}-specific prolyl-4 hydroxylase 2 but through activation of the NADPH oxidase/Rac pathway.

H.-Y. Lee, T. Lee, N. Lee, E. G. Yang, C. Lee, J. Lee, E.-Y. Moon, J. Ha, and H. Park (2011)
Carcinogenesis 32, 703-712
 |  Abstract »  |  Full Text »  |  PDF »

Normoxic Expression of Hypoxia-Inducible Factor 1 in Rat Leydig Cells In Vivo and In Vitro.

M. A. Palladino, P. R. Pirlamarla, J. McNamara, C. M. Sottas, N. Korah, M. P. Hardy, D. B. Hales, and L. Hermo (2011)
32, 307-323
 |  Abstract »  |  Full Text »  |  PDF »

Hypoxia Increases Sirtuin 1 Expression in a Hypoxia-inducible Factor-dependent Manner.

R. Chen, E. M. Dioum, R. T. Hogg, R. D. Gerard, and J. A. Garcia (2011)
J. Biol. Chem. 286, 13869-13878
 |  Abstract »  |  Full Text »  |  PDF »

Differential Sensitivity of Hypoxia Inducible Factor Hydroxylation Sites to Hypoxia and Hydroxylase Inhibitors.

Y.-M. Tian, K. K. Yeoh, M. K. Lee, T. Eriksson, B. M. Kessler, H. B. Kramer, M. J. Edelmann, C. Willam, C. W. Pugh, C. J. Schofield, et al. (2011)
J. Biol. Chem. 286, 13041-13051
 |  Abstract »  |  Full Text »  |  PDF »

Reversal of Experimental Renovascular Hypertension Restores Coronary Microvascular Function and Architecture.

V. H. Urbieta-Caceres, X.-Y. Zhu, M. E. Gibson, F. D. Favreau, K. Jordan, A. Lerman, and L. O. Lerman (2011)
Am J Hypertens 24, 458-465
 |  Abstract »  |  Full Text »  |  PDF »

Cardiomyocyte-specific Prolyl-4-hydroxylase Domain 2 Knock Out Protects from Acute Myocardial Ischemic Injury.

M. Holscher, M. Silter, S. Krull, M. von Ahlen, A. Hesse, P. Schwartz, B. Wielockx, G. Breier, D. M. Katschinski, and A. Zieseniss (2011)
J. Biol. Chem. 286, 11185-11194
 |  Abstract »  |  Full Text »  |  PDF »

Regulation of erythropoietin production.

W. Jelkmann (2011)
J. Physiol. 589, 1251-1258
 |  Abstract »  |  Full Text »  |  PDF »

Hypoxia. 2. Hypoxia regulates cellular metabolism.

W. W. Wheaton and N. S. Chandel (2011)
Am J Physiol Cell Physiol 300, C385-C393
 |  Abstract »  |  Full Text »  |  PDF »

Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility.

D. Astuti, C. J. Ricketts, R. Chowdhury, M. A. McDonough, D. Gentle, G. Kirby, S. Schlisio, R. S. Kenchappa, B. D. Carter, W. G. Kaelin Jr, et al. (2011)
Endocr. Relat. Cancer 18, 73-83
 |  Abstract »  |  Full Text »  |  PDF »

Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea.

J. B. J. Ward, K. Lawler, S. Amu, C. T. Taylor, P. G. Fallon, and S. J. Keely (2011)
FASEB J 25, 535-543
 |  Abstract »  |  Full Text »  |  PDF »

Regulation of Metabolism by Hypoxia-Inducible Factor 1.

G. L. Semenza (2011)
Cold Spring Harb Symp Quant Biol 76, 347-353
 |  Abstract »  |  Full Text »  |  PDF »

Autophagy, Stress, and Cancer Metabolism: What Doesn't Kill You Makes You Stronger.

R. Mathew and E. White (2011)
Cold Spring Harb Symp Quant Biol 76, 389-396
 |  Abstract »  |  Full Text »  |  PDF »

Deficiency of a Transmembrane Prolyl 4-Hydroxylase in the Zebrafish Leads to Basement Membrane Defects and Compromised Kidney Function.

J. Hyvarinen, M. Parikka, R. Sormunen, M. Ramet, K. Tryggvason, K. I. Kivirikko, J. Myllyharju, and P. Koivunen (2010)
J. Biol. Chem. 285, 42023-42032
 |  Abstract »  |  Full Text »  |  PDF »

PGC-1{alpha} regulates a HIF2{alpha}-dependent switch in skeletal muscle fiber types.

K. A. Rasbach, R. K. Gupta, J. L. Ruas, J. Wu, E. Naseri, J. L. Estall, and B. M. Spiegelman (2010)
PNAS 107, 21866-21871
 |  Abstract »  |  Full Text »  |  PDF »

On Getting There from Here.

S. L. McKnight (2010)
Science 330, 1338-1339
 |  Abstract »  |  Full Text »  |  PDF »

The Control of the Metabolic Switch in Cancers by Oncogenes and Tumor Suppressor Genes.

A. J. Levine and A. M. Puzio-Kuter (2010)
Science 330, 1340-1344
 |  Abstract »  |  Full Text »  |  PDF »

Novel Metastasis-Related Gene CIM Functions in the Regulation of Multiple Cellular Stress-Response Pathways.

K. Yanagisawa, H. Konishi, C. Arima, S. Tomida, T. Takeuchi, Y. Shimada, Y. Yatabe, T. Mitsudomi, H. Osada, and T. Takahashi (2010)
Cancer Res. 70, 9949-9958
 |  Abstract »  |  Full Text »  |  PDF »

Hypoxia-inducible factor regulates osteoclast-mediated bone resorption: role of angiopoietin-like 4.

H. J. Knowles, A.-M. Cleton-Jansen, E. Korsching, and N. A. Athanasou (2010)
FASEB J 24, 4648-4659
 |  Abstract »  |  Full Text »  |  PDF »

Mitochondrial reprogramming through cardiac oxygen sensors in ischaemic heart disease.

S. Cadenas, J. Aragones, and M. O. Landazuri (2010)
Cardiovasc Res 88, 219-228
 |  Abstract »  |  Full Text »  |  PDF »

Prolyl Hydroxylase Domain (PHD) 2 Affects Cell Migration and F-actin Formation via RhoA/Rho-associated Kinase-dependent Cofilin Phosphorylation.

S. Vogel, M. Wottawa, K. Farhat, A. Zieseniss, M. Schnelle, S. Le-Huu, M. von Ahlen, C. Malz, G. Camenisch, and D. M. Katschinski (2010)
J. Biol. Chem. 285, 33756-33763
 |  Abstract »  |  Full Text »  |  PDF »

Carbon Monoxide Promotes VEGF Expression by Increasing HIF-1{alpha} Protein Level via Two Distinct Mechanisms, Translational Activation and Stabilization of HIF-1{alpha} Protein.

Y. K. Choi, C.-K. Kim, H. Lee, D. Jeoung, K.-S. Ha, Y.-G. Kwon, K.-W. Kim, and Y.-M. Kim (2010)
J. Biol. Chem. 285, 32116-32125
 |  Abstract »  |  Full Text »  |  PDF »

Stabilization of Hypoxia-inducible Factor-1{alpha} Protein in Hypoxia Occurs Independently of Mitochondrial Reactive Oxygen Species Production.

Y. L. Chua, E. Dufour, E. P. Dassa, P. Rustin, H. T. Jacobs, C. T. Taylor, and T. Hagen (2010)
J. Biol. Chem. 285, 31277-31284
 |  Abstract »  |  Full Text »  |  PDF »

Balancing biosynthesis and bioenergetics: metabolic programs in oncogenesis.

J. F. Barger and D. R. Plas (2010)
Endocr. Relat. Cancer 17, R287-R304
 |  Abstract »  |  Full Text »  |  PDF »

Loss of Hypoxia-Inducible Factor Prolyl Hydroxylase Activity in Cardiomyocytes Phenocopies Ischemic Cardiomyopathy.

J. Moslehi, Y. A. Minamishima, J. Shi, D. Neuberg, D. M. Charytan, R. F. Padera, S. Signoretti, R. Liao, and W. G. Kaelin Jr (2010)
Circulation 122, 1004-1016
 |  Abstract »  |  Full Text »  |  PDF »

Altered Ferritin Subunit Composition: Change in Iron Metabolism in Lens Epithelial Cells and Downstream Effects on Glutathione Levels and VEGF Secretion.

J. Harned, J. Ferrell, M. M. Lall, L. N. Fleisher, S. Nagar, M. Goralska, and M. C. McGahan (2010)
Invest. Ophthalmol. Vis. Sci. 51, 4437-4446
 |  Abstract »  |  Full Text »  |  PDF »

Toxoplasma gondii Activates Hypoxia-inducible Factor (HIF) by Stabilizing the HIF-1{alpha} Subunit via Type I Activin-like Receptor Kinase Receptor Signaling.

M. Wiley, K. R. Sweeney, D. A. Chan, K. M. Brown, C. McMurtrey, E. W. Howard, A. J. Giaccia, and I. J. Blader (2010)
J. Biol. Chem. 285, 26852-26860
 |  Abstract »  |  Full Text »  |  PDF »

MicroRNAs Induced During Ischemic Preconditioning * Supplemental Methods.

S.-T. Lee, K. Chu, K.-H. Jung, H.-J. Yoon, D. Jeon, K.-M. Kang, K.-H. Park, E.-K. Bae, M. Kim, S. K. Lee, et al. (2010)
Stroke 41, 1646-1651
 |  Abstract »  |  Full Text »  |  PDF »

Inhibition of Hypoxia-inducible Factor-targeting Prolyl Hydroxylase Domain-containing Protein 2 (PHD2) Enhances Matrix Synthesis by Human Chondrocytes.

B. L. Thoms and C. L. Murphy (2010)
J. Biol. Chem. 285, 20472-20480
 |  Abstract »  |  Full Text »  |  PDF »

Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy.

K. G. Pringle, K. L. Kind, A. N. Sferruzzi-Perri, J. G. Thompson, and C. T. Roberts (2010)
Hum. Reprod. Update 16, 415-431
 |  Abstract »  |  Full Text »  |  PDF »

Hypoxic regulation of erythropoiesis and iron metabolism.

V. H. Haase (2010)
Am J Physiol Renal Physiol 299, F1-F13
 |  Abstract »  |  Full Text »  |  PDF »

Ascorbate Synthesis Pathway: DUAL ROLE OF ASCORBATE IN BONE HOMEOSTASIS.

K. H. Gabbay, K. M. Bohren, R. Morello, T. Bertin, J. Liu, and P. Vogel (2010)
J. Biol. Chem. 285, 19510-19520
 |  Abstract »  |  Full Text »  |  PDF »

Regulated oxygen sensing by protein hydroxylation in renal erythropoietin-producing cells.

R. H. Wenger and D. Hoogewijs (2010)
Am J Physiol Renal Physiol 298, F1287-F1296
 |  Abstract »  |  Full Text »  |  PDF »

Hypoxia-Inducible Factor Prolyl-Hydroxylase 2 Senses High-Salt Intake to Increase Hypoxia Inducible Factor 1{alpha} Levels in the Renal Medulla.

Z. Wang, Q. Zhu, M. Xia, P. L. Li, S. J. Hinton, and N. Li (2010)
Hypertension 55, 1129-1136
 |  Abstract »  |  Full Text »  |  PDF »

Hearts of Hypoxia-inducible Factor Prolyl 4-Hydroxylase-2 Hypomorphic Mice Show Protection against Acute Ischemia-Reperfusion Injury.

J. Hyvarinen, I. E. Hassinen, R. Sormunen, J. M. Maki, K. I. Kivirikko, P. Koivunen, and J. Myllyharju (2010)
J. Biol. Chem. 285, 13646-13657
 |  Abstract »  |  Full Text »  |  PDF »

Metabolic Shifts in Immunity and Inflammation.

D. J. Kominsky, E. L. Campbell, and S. P. Colgan (2010)
J. Immunol. 184, 4062-4068
 |  Abstract »  |  Full Text »  |  PDF »

Genome-wide identification of hypoxia-inducible factor binding sites and target genes by a probabilistic model integrating transcription-profiling data and in silico binding site prediction.

A. Ortiz-Barahona, D. Villar, N. Pescador, J. Amigo, and L. del Peso (2010)
Nucleic Acids Res. 38, 2332-2345
 |  Abstract »  |  Full Text »  |  PDF »

Nickel Ions Inhibit Histone Demethylase JMJD1A and DNA Repair Enzyme ABH2 by Replacing the Ferrous Iron in the Catalytic Centers.

H. Chen, N. C. Giri, R. Zhang, K. Yamane, Y. Zhang, M. Maroney, and M. Costa (2010)
J. Biol. Chem. 285, 7374-7383
 |  Abstract »  |  Full Text »  |  PDF »

Complex Regulation of the Transactivation Function of Hypoxia-inducible Factor-1{alpha} by Direct Interaction with Two Distinct Domains of the CREB-binding Protein/p300.

J. L. Ruas, U. Berchner-Pfannschmidt, S. Malik, K. Gradin, J. Fandrey, R. G. Roeder, T. Pereira, and L. Poellinger (2010)
J. Biol. Chem. 285, 2601-2609
 |  Abstract »  |  Full Text »  |  PDF »

Prolyl Hydroxylases 2 and 3 Act in Gliomas as Protective Negative Feedback Regulators of Hypoxia-Inducible Factors.

A.-T. Henze, J. Riedel, T. Diem, J. Wenner, I. Flamme, J. Pouyseggur, K. H. Plate, and T. Acker (2010)
Cancer Res. 70, 357-366
 |  Abstract »  |  Full Text »  |  PDF »

Structure Activity Analysis of 2-Methoxyestradiol Analogues Reveals Targeting of Microtubules as the Major Mechanism of Antiproliferative and Proapoptotic Activity.

Y. S. Chua, Y. L. Chua, and T. Hagen (2010)
Mol. Cancer Ther. 9, 224-235
 |  Abstract »  |  Full Text »  |  PDF »

Inhibition of Prolyl Hydroxylase Domain-Containing Protein Suppressed Lipopolysaccharide-Induced TNF-{alpha} Expression.

K. Takeda, T. Ichiki, E. Narabayashi, K. Inanaga, R. Miyazaki, T. Hashimoto, H. Matsuura, J. Ikeda, T. Miyata, and K. Sunagawa (2009)
Arterioscler Thromb Vasc Biol 29, 2132-2137
 |  Abstract »  |  Full Text »  |  PDF »

Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination, invasion, and metastasis in a zebrafish tumor model.

S. L. C. Lee, P. Rouhi, L. D. Jensen, D. Zhang, H. Ji, G. Hauptmann, P. Ingham, and Y. Cao (2009)
PNAS 106, 19485-19490
 |  Abstract »  |  Full Text »  |  PDF »

A Feedback Loop Involving the Phd3 Prolyl Hydroxylase Tunes the Mammalian Hypoxic Response In Vivo.

Y. A. Minamishima, J. Moslehi, R. F. Padera, R. T. Bronson, R. Liao, and W. G. Kaelin Jr. (2009)
Mol. Cell. Biol. 29, 5729-5741
 |  Abstract »  |  Full Text »  |  PDF »

Two Distinct Roles for EGL-9 in the Regulation of HIF-1-Mediated Gene Expression in Caenorhabditis elegans.

Z. Shao, Y. Zhang, and J. A. Powell-Coffman (2009)
Genetics 183, 821-829
 |  Abstract »  |  Full Text »  |  PDF »

The Crystal Structure of an Algal Prolyl 4-Hydroxylase Complexed with a Proline-rich Peptide Reveals a Novel Buried Tripeptide Binding Motif.

M. K. Koski, R. Hieta, M. Hirsila, A. Ronka, J. Myllyharju, and R. K. Wierenga (2009)
J. Biol. Chem. 284, 25290-25301
 |  Abstract »  |  Full Text »  |  PDF »

Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis.

G. L. Semenza (2009)
Blood 114, 2015-2019
 |  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 »

Central Role of the Oxygen-dependent Degradation Domain of Drosophila HIF{alpha}/Sima in Oxygen-dependent Nuclear Export.

M. Irisarri, S. Lavista-Llanos, N. M. Romero, L. Centanin, A. Dekanty, and P. Wappner (2009)
Mol. Biol. Cell 20, 3878-3887
 |  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 »

Fumarate Hydratase Deficiency in Renal Cancer Induces Glycolytic Addiction and Hypoxia-Inducible Transcription Factor 1{alpha} Stabilization by Glucose-Dependent Generation of Reactive Oxygen Species.

S. Sudarshan, C. Sourbier, H.-S. Kong, K. Block, V. A. V. Romero, Y. Yang, C. Galindo, M. Mollapour, B. Scroggins, N. Goode, et al. (2009)
Mol. Cell. Biol. 29, 4080-4090
 |  Abstract »  |  Full Text »  |  PDF »

Metabolic transformation in cancer.

D. A. Tennant, R. V. Duran, H. Boulahbel, and E. Gottlieb (2009)
Carcinogenesis 30, 1269-1280
 |  Abstract »  |  Full Text »  |  PDF »

Selective Inhibition of Hypoxia-Inducible Factor (HIF) Prolyl-Hydroxylase 1 Mediates Neuroprotection against Normoxic Oxidative Death via HIF- and CREB-Independent Pathways.

A. Siddiq, L. R. Aminova, C. M. Troy, K. Suh, Z. Messer, G. L. Semenza, and R. R. Ratan (2009)
J. Neurosci. 29, 8828-8838
 |  Abstract »  |  Full Text »  |  PDF »

Oxygen-Regulated {beta}2-Adrenergic Receptor Hydroxylation by EGLN3 and Ubiquitylation by pVHL.

L. Xie, K. Xiao, E. J. Whalen, M. T. Forrester, R. S. Freeman, G. Fong, S. P. Gygi, R. J. Lefkowitz, and J. S. Stamler (2009)
Science Signaling 2, ra33
 |  Abstract »  |  Full Text »  |  PDF »

Inhibition of Prolyl Hydroxylase Domain Proteins Promotes Therapeutic Revascularization.

C. Loinard, A. Ginouves, J. Vilar, C. Cochain, Y. Zouggari, A. Recalde, M. Duriez, B. I. Levy, J. Pouyssegur, E. Berra, et al. (2009)
Circulation 120, 50-59
 |  Abstract »  |  Full Text »  |  PDF »

Increased prolyl 4-hydroxylase expression and differential regulation of hypoxia-inducible factors in the aged rat brain.

O. I. Ndubuizu, J. C. Chavez, and J. C. LaManna (2009)
Am J Physiol Regulatory Integrative Comp Physiol 297, R158-R165
 |  Abstract »  |  Full Text »  |  PDF »

Arachidonic acid potentiates hypoxia-induced VEGF expression in mouse embryonic stem cells: involvement of Notch, Wnt, and HIF-1{alpha}.

S. H. Lee, M. H. Kim, and H. J. Han (2009)
Am J Physiol Cell Physiol 297, C207-C216
 |  Abstract »  |  Full Text »  |  PDF »

Hypoxia Inducible Factor-2{alpha} Stabilization and Maxi-K+ Channel {beta}1-Subunit Gene Repression by Hypoxia in Cardiac Myocytes: Role in Preconditioning.

L. Bautista, M. J. Castro, J. Lopez-Barneo, and A. Castellano (2009)
Circ. Res. 104, 1364-1372
 |  Abstract »  |  Full Text »  |  PDF »