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.


Logo for

Genes & Dev. 15 (20): 2675-2686

Copyright © 2001 by Cold Spring Harbor Laboratory Press.

Vol. 15, No. 20, pp. 2675-2686, October 15, 2001

FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity

Patrick C. Mahon,1,3 Kiichi Hirota,1,2,3 and Gregg L. Semenza1,4

1 Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3914, USA; 2 Department of Anesthesia, Kyoto University Hospital, Kyoto University, Kyoto, 606-8507, Japan

Hypoxia-inducible factor 1 (HIF-1) is a master regulator of oxygen homeostasis that controls angiogenesis, erythropoiesis, and glycolysis via transcriptional activation of target genes under hypoxic conditions. O2-dependent binding of the von Hippel-Lindau (VHL) tumor suppressor protein targets the HIF-1alpha subunit for ubiquitination and proteasomal degradation. The activity of the HIF-1alpha transactivation domains is also O2 regulated by a previously undefined mechanism. Here, we report the identification of factor inhibiting HIF-1 (FIH-1), a protein that binds to HIF-1alpha and inhibits its transactivation function. In addition, we demonstrate that FIH-1 binds to VHL and that VHL also functions as a transcriptional corepressor that inhibits HIF-1alpha transactivation function by recruiting histone deacetylases. Involvement of VHL in association with FIH-1 provides a unifying mechanism for the modulation of HIF-1alpha protein stabilization and transcriptional activation in response to changes in cellular O2 concentration.

[Key Words: Corepressor; histone deacetylase; hypoxia; transactivation]

3 These authors contributed equally to this work.

4 Corresponding author.

GENES & DEVELOPMENT 15:2675-2686 © 2001 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/01 $5.00

HIF and pulmonary vascular responses to hypoxia.
L. A. Shimoda and S. S. Laurie (2014)
J Appl Physiol 116, 867-874
   Abstract »    Full Text »    PDF »
EAF2 Suppresses Hypoxia-Induced Factor 1{alpha} Transcriptional Activity by Disrupting Its Interaction with Coactivator CBP/p300.
Z. Chen, X. Liu, Z. Mei, Z. Wang, and W. Xiao (2014)
Mol. Cell. Biol. 34, 1085-1099
   Abstract »    Full Text »    PDF »
The role of angiogenic factors in fibroid pathogenesis: potential implications for future therapy.
R. Tal and J. H. Segars (2014)
Hum. Reprod. Update 20, 194-216
   Abstract »    Full Text »    PDF »
Hypoxia-Inducible Factor 1 Regulation through Cross Talk between mTOR and MT1-MMP.
T. Sakamoto, J. S. Weng, T. Hara, S. Yoshino, H. Kozuka-Hata, M. Oyama, and M. Seiki (2014)
Mol. Cell. Biol. 34, 30-42
   Abstract »    Full Text »    PDF »
Restricted Expression of miR-30c-2-3p and miR-30a-3p in Clear Cell Renal Cell Carcinomas Enhances HIF2{alpha} Activity.
L. K. Mathew, S. S. Lee, N. Skuli, S. Rao, B. Keith, K. L. Nathanson, P. Lal, and M. C. Simon (2014)
Cancer Discovery 4, 53-60
   Abstract »    Full Text »    PDF »
Interaction of HIF-1{alpha} and Notch3 Is Required for the Expression of Carbonic Anhydrase 9 in Breast Carcinoma Cells.
M. M. Shareef, T. S. Udayakumar, V. K. Sinha, S. M. Saleem, and W. W. Griggs (2013)
Genes & Cancer 4, 513-523
   Abstract »    Full Text »    PDF »
The gut in iron homeostasis: role of HIF-2 under normal and pathological conditions.
M. Mastrogiannaki, P. Matak, and C. Peyssonnaux (2013)
Blood 122, 885-892
   Abstract »    Full Text »    PDF »
Factor inhibiting HIF-1 (FIH-1) modulates protein interactions of apoptosis-stimulating p53 binding protein 2 (ASPP2).
K. Janke, U. Brockmeier, K. Kuhlmann, M. Eisenacher, J. Nolde, H. E. Meyer, H. Mairbaurl, and E. Metzen (2013)
J. Cell Sci. 126, 2629-2640
   Abstract »    Full Text »    PDF »
FIH-1/c-Kit Signaling: A Novel Contributor to Corneal Epithelial Glycogen Metabolism.
H. Peng, J. Katsnelson, W. Yang, M. A. Brown, and R. M. Lavker (2013)
Invest. Ophthalmol. Vis. Sci. 54, 2781-2786
   Abstract »    Full Text »    PDF »
What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer.
J.-A. Losman and W. G. Kaelin Jr. (2013)
Genes & Dev. 27, 836-852
   Abstract »    Full Text »    PDF »
Activation of hypoxia-inducible factor-1 in pulmonary arterial smooth muscle cells by endothelin-1.
S. Pisarcik, J. Maylor, W. Lu, X. Yun, C. Undem, J. T. Sylvester, G. L. Semenza, and L. A. Shimoda (2013)
Am J Physiol Lung Cell Mol Physiol 304, L549-L561
   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 »
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 »
Hypoxic adaptation engages the CBP/CREST-induced coactivator complex of Creb-HIF-1{alpha} in transactivating murine neuroblastic glucose transporter.
S. Thamotharan, N. Raychaudhuri, M. Tomi, B.-C. Shin, and S. U. Devaskar (2013)
Am J Physiol Endocrinol Metab 304, E583-E598
   Abstract »    Full Text »    PDF »
H. F. Bunn (2013)
Cold Spring Harb Perspect Med 3, a011619
   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 »
Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression.
W. Luo, R. Chang, J. Zhong, A. Pandey, and G. L. Semenza (2012)
PNAS 109, E3367-E3376
   Abstract »    Full Text »    PDF »
55th Bowditch Lecture: Effects of chronic hypoxia on the pulmonary circulation: Role of HIF-1.
L. A. Shimoda (2012)
J Appl Physiol 113, 1343-1352
   Abstract »    Full Text »    PDF »
The TNF-{alpha}/ROS/HIF-1-induced Upregulation of FoxMI Expression Promotes HCC Proliferation and Resistance to Apoptosis.
L. Xia, P. Mo, W. Huang, L. Zhang, Y. Wang, H. Zhu, D. Tian, J. Liu, Z. Chen, Y. Zhang, et al. (2012)
Carcinogenesis 33, 2250-2259
   Abstract »    Full Text »    PDF »
HIF1{alpha} Protein Stability Is Increased by Acetylation at Lysine 709.
H. Geng, Q. Liu, C. Xue, L. L. David, T. M. Beer, G. V. Thomas, M.-S. Dai, and D. Z. Qian (2012)
J. Biol. Chem. 287, 35496-35505
   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 »
microRNA-31/factor-inhibiting hypoxia-inducible factor 1 nexus regulates keratinocyte differentiation.
H. Peng, N. Kaplan, R. B. Hamanaka, J. Katsnelson, H. Blatt, W. Yang, L. Hao, P. J. Bryar, R. S. Johnson, S. Getsios, et al. (2012)
PNAS 109, 14030-14034
   Abstract »    Full Text »    PDF »
Identification and Proteomic Analysis of Distinct UBE3A/E6AP Protein Complexes.
G. Martinez-Noel, J. T. Galligan, M. E. Sowa, V. Arndt, T. M. Overton, J. W. Harper, and P. M. Howley (2012)
Mol. Cell. Biol. 32, 3095-3106
   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 »
MT1-MMP plays a critical role in hematopoiesis by regulating HIF-mediated chemokine/cytokine gene transcription within niche cells.
C. Nishida, K. Kusubata, Y. Tashiro, I. Gritli, A. Sato, M. Ohki-Koizumi, Y. Morita, M. Nagano, T. Sakamoto, N. Koshikawa, et al. (2012)
Blood 119, 5405-5416
   Abstract »    Full Text »    PDF »
HIF-1{alpha} deletion partially rescues defects of hematopoietic stem cell quiescence caused by Cited2 deficiency.
J. Du, Y. Chen, Q. Li, X. Han, C. Cheng, Z. Wang, D. Danielpour, S. L. Dunwoodie, K. D. Bunting, and Y.-C. Yang (2012)
Blood 119, 2789-2798
   Abstract »    Full Text »    PDF »
Factor Inhibiting HIF (FIH) Recognizes Distinct Molecular Features within Hypoxia-inducible Factor-{alpha} (HIF-{alpha}) versus Ankyrin Repeat Substrates.
S. E. Wilkins, S. Karttunen, R. J. Hampton-Smith, I. Murchland, A. Chapman-Smith, and D. J. Peet (2012)
J. Biol. Chem. 287, 8769-8781
   Abstract »    Full Text »    PDF »
Synthetic transactivation screening reveals ETV4 as broad coactivator of hypoxia-inducible factor signaling.
K. Wollenick, J. Hu, G. Kristiansen, P. Schraml, H. Rehrauer, U. Berchner-Pfannschmidt, J. Fandrey, R. H. Wenger, and D. P. Stiehl (2012)
Nucleic Acids Res. 40, 1928-1943
   Abstract »    Full Text »    PDF »
The Ubiquitin-Proteasome System Meets Angiogenesis.
N. Rahimi (2012)
Mol. Cancer Ther. 11, 538-548
   Abstract »    Full Text »    PDF »
Four-and-a-Half LIM Domain Proteins Inhibit Transactivation by Hypoxia-inducible Factor 1.
M. E. Hubbi, D. M. Gilkes, J. H. Baek, and G. L. Semenza (2012)
J. Biol. Chem. 287, 6139-6149
   Abstract »    Full Text »    PDF »
Hypoxia-Induced Angiogenesis: Good and Evil.
B. L. Krock, N. Skuli, and M. C. Simon (2011)
Genes & Cancer 2, 1117-1133
   Abstract »    Full Text »    PDF »
Generation of a Mouse Model of Von Hippel-Lindau Kidney Disease Leading to Renal Cancers by Expression of a Constitutively Active Mutant of HIF1{alpha}.
L. Fu, G. Wang, M. M. Shevchuk, D. M. Nanus, and L. J. Gudas (2011)
Cancer Res. 71, 6848-6856
   Abstract »    Full Text »    PDF »
The chromatin remodeler ISWI regulates the cellular response to hypoxia: role of FIH.
A. Melvin, S. Mudie, and S. Rocha (2011)
Mol. Biol. Cell 22, 4171-4181
   Abstract »    Full Text »    PDF »
Quantitative Mass Spectrometry Reveals Dynamics of Factor-inhibiting Hypoxia-inducible Factor-catalyzed Hydroxylation.
R. S. Singleton, D. C. Trudgian, R. Fischer, B. M. Kessler, P. J. Ratcliffe, and M. E. Cockman (2011)
J. Biol. Chem. 286, 33784-33794
   Abstract »    Full Text »    PDF »
Deletion of the Mint3/Apba3 Gene in Mice Abrogates Macrophage Functions and Increases Resistance to Lipopolysaccharide-induced Septic Shock.
T. Hara, K. Mimura, T. Abe, G. Shioi, M. Seiki, and T. Sakamoto (2011)
J. Biol. Chem. 286, 32542-32551
   Abstract »    Full Text »    PDF »
VHL Gene Mutations and Their Effects on Hypoxia Inducible Factor HIF{alpha}: Identification of Potential Driver and Passenger Mutations.
M. P. Rechsteiner, A. von Teichman, A. Nowicka, T. Sulser, P. Schraml, and H. Moch (2011)
Cancer Res. 71, 5500-5511
   Abstract »    Full Text »    PDF »
Normoxic Activation of Hypoxia-Inducible Factors in Photoreceptors Provides Transient Protection against Light-Induced Retinal Degeneration.
C. Lange, S. R. Heynen, N. Tanimoto, M. Thiersch, Y.-Z. Le, I. Meneau, M. W. Seeliger, M. Samardzija, C. Caprara, and C. Grimm (2011)
Invest. Ophthalmol. Vis. Sci. 52, 5872-5880
   Abstract »    Full Text »    PDF »
Spinal Vascular Endothelial Growth Factor Induces Phrenic Motor Facilitation via Extracellular Signal-Regulated Kinase and Akt Signaling.
E. A. Dale-Nagle, I. Satriotomo, and G. S. Mitchell (2011)
J. Neurosci. 31, 7682-7690
   Abstract »    Full Text »    PDF »
Regulation of HIF-1{alpha} activity in adipose tissue by obesity-associated factors: adipogenesis, insulin, and hypoxia.
Q. He, Z. Gao, J. Yin, J. Zhang, Z. Yun, and J. Ye (2011)
Am J Physiol Endocrinol Metab 300, E877-E885
   Abstract »    Full Text »    PDF »
Targeting the Warburg Effect That Arises in Tumor Cells Expressing Membrane Type-1 Matrix Metalloproteinase.
T. Sakamoto, D. Niiya, and M. Seiki (2011)
J. Biol. Chem. 286, 14691-14704
   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 »
Regulation of erythropoietin production.
W. Jelkmann (2011)
J. Physiol. 589, 1251-1258
   Abstract »    Full Text »    PDF »
Asparagine and Aspartate Hydroxylation of the Cytoskeletal Ankyrin Family Is Catalyzed by Factor-inhibiting Hypoxia-inducible Factor.
M. Yang, W. Ge, R. Chowdhury, T. D. W. Claridge, H. B. Kramer, B. Schmierer, M. A. McDonough, L. Gong, B. M. Kessler, P. J. Ratcliffe, et al. (2011)
J. Biol. Chem. 286, 7648-7660
   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 »
From Vessel Sprouting to Normalization: Role of the Prolyl Hydroxylase Domain Protein/Hypoxia-Inducible Factor Oxygen-Sensing Machinery.
C. Coulon, M. Georgiadou, C. Roncal, K. De Bock, T. Langenberg, and P. Carmeliet (2010)
Arterioscler Thromb Vasc Biol 30, 2331-2336
   Abstract »    Full Text »    PDF »
Ancient Atmospheres and the Evolution of Oxygen Sensing Via the Hypoxia-Inducible Factor in Metazoans.
C. T. Taylor and J. C. McElwain (2010)
Physiology 25, 272-279
   Abstract »    Full Text »    PDF »
HIF-1 mediates pathogenic inflammatory responses to intestinal ischemia-reperfusion injury.
R. Feinman, E. A. Deitch, A. C. Watkins, B. Abungu, I. Colorado, K. B. Kannan, S. U. Sheth, F. J. Caputo, Q. Lu, M. Ramanathan, et al. (2010)
Am J Physiol Gastrointest Liver Physiol 299, G833-G843
   Abstract »    Full Text »    PDF »
A Membrane Protease Regulates Energy Production in Macrophages by Activating Hypoxia-inducible Factor-1 via a Non-proteolytic Mechanism.
T. Sakamoto and M. Seiki (2010)
J. Biol. Chem. 285, 29951-29964
   Abstract »    Full Text »    PDF »
Chronic reduction in cardiac output induces hypoxic signaling in larval zebrafish even at a time when convective oxygen transport is not required.
R. Kopp, T. Schwerte, M. Egg, A. M. Sandbichler, B. Egger, and B. Pelster (2010)
Physiol Genomics 42A, 8-23
   Abstract »    Full Text »    PDF »
Profile of Gregg L. Semenza.
F. Ahmed (2010)
PNAS 107, 14521-14523
   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 »
HIF-2{alpha}-mediated activation of the epidermal growth factor receptor potentiates head and neck cancer cell migration in response to hypoxia.
X. Wang and A. Schneider (2010)
Carcinogenesis 31, 1202-1210
   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 »
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-1-dependent mechanisms of vascularization and vascular remodelling.
S. Rey and G. L. Semenza (2010)
Cardiovasc Res 86, 236-242
   Abstract »    Full Text »    PDF »
Prolyl Hydroxylase EGLN3 Regulates Skeletal Myoblast Differentiation through an NF-{kappa}B-dependent Pathway.
J. Fu and M. B. Taubman (2010)
J. Biol. Chem. 285, 8927-8935
   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 »
Hypoxic Repression of Endothelial Nitric-oxide Synthase Transcription Is Coupled with Eviction of Promoter Histones.
J. E. Fish, M. S. Yan, C. C. Matouk, R. St. Bernard, J. J. D. Ho, A. Gavryushova, D. Srivastava, and P. A. Marsden (2010)
J. Biol. Chem. 285, 810-826
   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 »
Mint3 Enhances the Activity of Hypoxia-inducible Factor-1 (HIF-1) in Macrophages by Suppressing the Activity of Factor Inhibiting HIF-1.
T. Sakamoto and M. Seiki (2009)
J. Biol. Chem. 284, 30350-30359
   Abstract »    Full Text »    PDF »
Nutlin-3, an Hdm2 antagonist, inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated inactivation of HIF-1{alpha}.
Y.-M. Lee, J.-H. Lim, Y.-S. Chun, H.-E. Moon, M. K. Lee, L.E. Huang, and J.-W. Park (2009)
Carcinogenesis 30, 1768-1775
   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 »
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 »
Regulation of Hypoxia-Inducible Factor 2{alpha} Signaling by the Stress-Responsive Deacetylase Sirtuin 1.
E. M. Dioum, R. Chen, M. S. Alexander, Q. Zhang, R. T. Hogg, R. D. Gerard, and J. A. Garcia (2009)
Science 324, 1289-1293
   Abstract »    Full Text »    PDF »
SEPT9_v1 Up-regulates Hypoxia-inducible Factor 1 by Preventing Its RACK1-mediated Degradation.
S. Amir, R. Wang, J. W. Simons, and N. J. Mabjeesh (2009)
J. Biol. Chem. 284, 11142-11151
   Abstract »    Full Text »    PDF »
Regulation of Oxygen Homeostasis by Hypoxia-Inducible Factor 1.
G. L. Semenza (2009)
Physiology 24, 97-106
   Abstract »    Full Text »    PDF »
Melanoma Antigen-11 Inhibits the Hypoxia-Inducible Factor Prolyl Hydroxylase 2 and Activates Hypoxic Response.
O. Aprelikova, S. Pandolfi, S. Tackett, M. Ferreira, K. Salnikow, Y. Ward, J. I. Risinger, J. C. Barrett, and J. Niederhuber (2009)
Cancer Res. 69, 616-624
   Abstract »    Full Text »    PDF »
Copper Regulation of Hypoxia-Inducible Factor-1 Activity.
W. Feng, F. Ye, W. Xue, Z. Zhou, and Y. J. Kang (2009)
Mol. Pharmacol. 75, 174-182
   Abstract »    Full Text »    PDF »
The Histone Demethylases JMJD1A and JMJD2B Are Transcriptional Targets of Hypoxia-inducible Factor HIF.
S. Beyer, M. M. Kristensen, K. S. Jensen, J. V. Johansen, and P. Staller (2008)
J. Biol. Chem. 283, 36542-36552
   Abstract »    Full Text »    PDF »
A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation from HIF-1{alpha}.
S. H. Li, D. H. Shin, Y.-S. Chun, M. K. Lee, M.-S. Kim, and J.-W. Park (2008)
Mol. Cancer Ther. 7, 3729-3738
   Abstract »    Full Text »    PDF »
Nuclear Oxygen Sensing: Induction of Endogenous Prolyl-hydroxylase 2 Activity by Hypoxia and Nitric Oxide.
U. Berchner-Pfannschmidt, S. Tug, B. Trinidad, F. Oehme, H. Yamac, C. Wotzlaw, I. Flamme, and J. Fandrey (2008)
J. Biol. Chem. 283, 31745-31753
   Abstract »    Full Text »    PDF »
Transcriptional Activation of HIF-1 by ROR{alpha} and its Role in Hypoxia Signaling.
E.-J. Kim, Y.-G. Yoo, W.-K. Yang, Y.-S. Lim, T.-Y. Na, I.-K. Lee, and M.-O. Lee (2008)
Arterioscler Thromb Vasc Biol 28, 1796-1802
   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 »
(2R)-[(4-Biphenylylsulfonyl)amino]-N-hydroxy-3-phenylpropionamide (BiPS), a Matrix Metalloprotease Inhibitor, Is a Novel and Potent Activator of Hypoxia-Inducible Factors.
M.-C. Lauzier, G. A. Robitaille, D. A. Chan, A. J. Giaccia, and D. E. Richard (2008)
Mol. Pharmacol. 74, 282-288
   Abstract »    Full Text »    PDF »
Bortezomib inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated repression of hypoxia-inducible factor-1.
D. H. Shin, Y.-S. Chun, D. S. Lee, L. E. Huang, and J.-W. Park (2008)
Blood 111, 3131-3136
   Abstract »    Full Text »    PDF »
Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure.
Y. A. Minamishima, J. Moslehi, N. Bardeesy, D. Cullen, R. T. Bronson, and W. G. Kaelin Jr (2008)
Blood 111, 3236-3244
   Abstract »    Full Text »    PDF »
Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways.
X. Zheng, S. Linke, J. M. Dias, X. Zheng, K. Gradin, T. P. Wallis, B. R. Hamilton, M. Gustafsson, J. L. Ruas, S. Wilkins, et al. (2008)
PNAS 105, 3368-3373
   Abstract »    Full Text »    PDF »
NDRG1, a growth and cancer related gene: regulation of gene expression and function in normal and disease states.
T. P. Ellen, Q. Ke, P. Zhang, and M. Costa (2008)
Carcinogenesis 29, 2-8
   Abstract »    Full Text »    PDF »
Calcineurin Promotes Hypoxia-inducible Factor 1{alpha} Expression by Dephosphorylating RACK1 and Blocking RACK1 Dimerization.
Y. V. Liu, M. E. Hubbi, F. Pan, K. R. McDonald, M. Mansharamani, R. N. Cole, J. O. Liu, and G. L. Semenza (2007)
J. Biol. Chem. 282, 37064-37073
   Abstract »    Full Text »    PDF »
Spermidine/Spermine N1-Acetyltransferase-1 Binds to Hypoxia-inducible Factor-1{alpha} (HIF-1{alpha}) and RACK1 and Promotes Ubiquitination and Degradation of HIF-1{alpha}.
J. H. Baek, Y. V. Liu, K. R. McDonald, J. B. Wesley, H. Zhang, and G. L. Semenza (2007)
J. Biol. Chem. 282, 33358-33366
   Abstract »    Full Text »    PDF »
The N-Terminal Transactivation Domain Confers Target Gene Specificity of Hypoxia-inducible Factors HIF-1{alpha} and HIF-2{alpha}.
C.-J. Hu, A. Sataur, L. Wang, H. Chen, and M. C. Simon (2007)
Mol. Biol. Cell 18, 4528-4542
   Abstract »    Full Text »    PDF »
Protein Kinase C-Mediated Modulation of FIH-1 Expression by the Homeodomain Protein CDP/Cut/Cux.
J. Li, E. Wang, S. Dutta, J. S. Lau, S.-w. Jiang, K. Datta, and D. Mukhopadhyay (2007)
Mol. Cell. Biol. 27, 7345-7353
   Abstract »    Full Text »    PDF »
Effect of chemical stabilizers of hypoxia-inducible factors on early lung development.
F. A. Groenman, M. Rutter, J. Wang, I. Caniggia, D. Tibboel, and M. Post (2007)
Am J Physiol Lung Cell Mol Physiol 293, L557-L567
   Abstract »    Full Text »    PDF »
Spermidine/Spermine-N1-Acetyltransferase 2 Is an Essential Component of the Ubiquitin Ligase Complex That Regulates Hypoxia-inducible Factor 1{alpha}.
J. H. Baek, Y. V. Liu, K. R. McDonald, J. B. Wesley, M. E. Hubbi, H. Byun, and G. L. Semenza (2007)
J. Biol. Chem. 282, 23572-23580
   Abstract »    Full Text »    PDF »
The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production.
E. L. Bell, T. A. Klimova, J. Eisenbart, C. T. Moraes, M. P. Murphy, G.R. S. Budinger, and N. S. Chandel (2007)
J. Cell Biol. 177, 1029-1036
   Abstract »    Full Text »    PDF »
The Peptidyl Prolyl cis/trans Isomerase FKBP38 Determines Hypoxia-Inducible Transcription Factor Prolyl-4-Hydroxylase PHD2 Protein Stability.
S. Barth, J. Nesper, P. A. Hasgall, R. Wirthner, K. J. Nytko, F. Edlich, D. M. Katschinski, D. P. Stiehl, R. H. Wenger, and G. Camenisch (2007)
Mol. Cell. Biol. 27, 3758-3768
   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 »
The Hypoxia-Inducible Factor 2{alpha} N-Terminal and C-Terminal Transactivation Domains Cooperate To Promote Renal Tumorigenesis In Vivo.
Q. Yan, S. Bartz, M. Mao, L. Li, and W. G. Kaelin Jr. (2007)
Mol. Cell. Biol. 27, 2092-2102
   Abstract »    Full Text »    PDF »
Histone Deacetylase Inhibitors Synergize p300 Autoacetylation that Regulates Its Transactivation Activity and Complex Formation.
D. P. Stiehl, D. M. Fath, D. Liang, Y. Jiang, and N. Sang (2007)
Cancer Res. 67, 2256-2264
   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