Genomes and Genes
Gene Symbol: HIF-1 alpha
Description: hypoxia inducible factor 1 subunit alpha
Alias: HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1, PASD8, bHLHe78, hypoxia-inducible factor 1-alpha, ARNT interacting protein, PAS domain-containing protein 8, basic-helix-loop-helix-PAS protein MOP1, class E basic helix-loop-helix protein 78, hypoxia inducible factor 1 alpha subunit, hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor), hypoxia-inducible factor 1 alpha isoform I.3, hypoxia-inducible factor1alpha, member of PAS protein 1, member of PAS superfamily 1
Products: HIF-1 alpha
Publications538 found, 100 shown here
- Forsythe J, Jiang B, Iyer N, Agani F, Leung S, Koos R, et al. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996;16:4604-13 pubmed..VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. These findings implicate HIF-1 in the activation of VEGF transcription in hypoxic cells. ..
- Liu X, Kirschenbaum A, Lu M, Yao S, Dosoretz A, Holland J, et al. Prostaglandin E2 induces hypoxia-inducible factor-1alpha stabilization and nuclear localization in a human prostate cancer cell line. J Biol Chem. 2002;277:50081-6 pubmed
- Löfstedt T, Jögi A, Sigvardsson M, Gradin K, Poellinger L, Påhlman S, et al. Induction of ID2 expression by hypoxia-inducible factor-1: a role in dedifferentiation of hypoxic neuroblastoma cells. J Biol Chem. 2004;279:39223-31 pubmed..Hypoxia-induced ID2 expression could play a significant role in the previously observed dedifferentiation of hypoxic neuroblastoma cells, which in a clinical setting could lead to less mature and more aggressive tumors. ..
- Berchner Pfannschmidt U, Petrat F, Doege K, Trinidad B, Freitag P, Metzen E, et al. Chelation of cellular calcium modulates hypoxia-inducible gene expression through activation of hypoxia-inducible factor-1alpha. J Biol Chem. 2004;279:44976-86 pubmed..Instead, effective chelation of cellular calcium caused the accumulation of HIF-1alpha protein through inhibition of HIF-prolyl hydroxylases and activated HIF-1-dependent gene expression under normoxic conditions. ..
- Kim J, Gao P, Liu Y, Semenza G, Dang C. Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol Cell Biol. 2007;27:7381-93 pubmed
- Wang G, Jiang B, Rue E, Semenza G. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995;92:5510-4 pubmed
- Demidenko Z, Rapisarda A, Garayoa M, Giannakakou P, Melillo G, Blagosklonny M. Accumulation of hypoxia-inducible factor-1alpha is limited by transcription-dependent depletion. Oncogene. 2005;24:4829-38 pubmed..But under hypoxia, HIF-1alpha accumulates and transcriptionally activates its own degradation that is independent from the PHD/VHL pathway. ..
- Klatte T, Seligson D, Riggs S, Leppert J, Berkman M, Kleid M, et al. Hypoxia-inducible factor 1 alpha in clear cell renal cell carcinoma. Clin Cancer Res. 2007;13:7388-93 pubmed..Because HIF-1 alpha and CAIX are independently and differentially regulated in metastatic clear cell RCC, both tumor markers can be complementary in predicting prognosis. ..
- Wan C, Gilbert S, Wang Y, Cao X, Shen X, Ramaswamy G, et al. Activation of the hypoxia-inducible factor-1alpha pathway accelerates bone regeneration. Proc Natl Acad Sci U S A. 2008;105:686-91 pubmed publisher..These results identify the HIF-1alpha pathway as a critical mediator of neoangiogenesis required for skeletal regeneration and suggest the application of HIF activators as therapies to improve bone healing. ..
- Emerling B, Weinberg F, Liu J, Mak T, Chandel N. PTEN regulates p300-dependent hypoxia-inducible factor 1 transcriptional activity through Forkhead transcription factor 3a (FOXO3a). Proc Natl Acad Sci U S A. 2008;105:2622-7 pubmed publisher..Coimmunoprecipitation and GAL4-HIF-1alpha transactivation assays reveal that FOXO3a interferes with p300-dependent HIF-1 transcriptional activity. Thus, FOXO3a negatively regulates HIF-1 transcriptional activity. ..
- Xue Y, Li N, Yang J, Chen Y, Yang L, Liu W. Phosphatidylinositol 3'-kinase signaling pathway is essential for Rac1-induced hypoxia-inducible factor-1(alpha) and vascular endothelial growth factor expression. Am J Physiol Heart Circ Physiol. 2011;300:H2169-76 pubmed publisher..Rac1-mediated inhibition of p53 and VHL could therefore be implicated in the upregulation of HIF-1? expression. ..
- Ruiz Tovar J, Fernández Contreras M, Martín Pérez E, Gamallo C. Association of thymidylate synthase and hypoxia inducible factor-1alpha DNA polymorphisms with pancreatic cancer. Tumori. 2012;98:364-9 pubmed publisher..In the present study, we investigated the effect of three DNA polymorphisms within the thymidylate synthase gene and two within hypoxia inducible factor-1? on the prognosis of pancreatic cancer...
- Gray M, Zhang J, Ellis L, Semenza G, Evans D, Watowich S, et al. HIF-1alpha, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas. Oncogene. 2005;24:3110-20 pubmed..These data suggest that the binding of both STAT3 and HIF-1alpha to the VEGF promoter is required for maximum transcription of VEGF mRNA following hypoxia. ..
- Moon H, Cheon H, Chun K, Lee S, Kim Y, Jung B, et al. Metastasis-associated protein 1 enhances angiogenesis by stabilization of HIF-1alpha. Oncol Rep. 2006;16:929-35 pubmed..These results indicate that MTA1 enhances angiogenesis by stabilization of the HIF-1alpha protein, which is closely related to the increased metastatic potential of cancer cells with high MTA1 expression. ..
- Zhao S, Lin Y, Xu W, Jiang W, Zha Z, Wang P, et al. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science. 2009;324:261-5 pubmed publisher..Thus, IDH1 appears to function as a tumor suppressor that, when mutationally inactivated, contributes to tumorigenesis in part through induction of the HIF-1 pathway. ..
- Herr B, Zhou J, Werno C, Menrad H, Namgaladze D, Weigert A, et al. The supernatant of apoptotic cells causes transcriptional activation of hypoxia-inducible factor-1alpha in macrophages via sphingosine-1-phosphate and transforming growth factor-beta. Blood. 2009;114:2140-8 pubmed publisher..This shows the importance of HIF-1-elicited responses in regulatory macrophages under normoxia. ..
- Cook K, Hilton S, Mecinovic J, Motherwell W, Figg W, Schofield C. Epidithiodiketopiperazines block the interaction between hypoxia-inducible factor-1alpha (HIF-1alpha) and p300 by a zinc ejection mechanism. J Biol Chem. 2009;284:26831-8 pubmed publisher..The results have implications for the design of selective ETPs and for the interaction of ETPs with other zinc ion-binding protein targets involved in gene expression. ..
- Brouwer E, Gouw A, Posthumus M, van Leeuwen M, Boerboom A, Bijzet J, et al. Hypoxia inducible factor-1-alpha (HIF-1alpha) is related to both angiogenesis and inflammation in rheumatoid arthritis. Clin Exp Rheumatol. 2009;27:945-51 pubmed..These results thus suggest that HIF-1alpha could serve as an important new therapeutic target in RA, targeting both angiogenesis and inflammation. ..
- Alfranca A, Gutiérrez M, Vara A, Aragones J, Vidal F, Landazuri M. c-Jun and hypoxia-inducible factor 1 functionally cooperate in hypoxia-induced gene transcription. Mol Cell Biol. 2002;22:12-22 pubmed..The functional interplay between c-Jun and HIF-1 provides a novel insight into the regulation of some genes, such as the one for VEGF, which is a key regulator of tumor angiogenesis. ..
- Acs G, Xu X, Chu C, Acs P, Verma A. Prognostic significance of erythropoietin expression in human endometrial carcinoma. Cancer. 2004;100:2376-86 pubmed..Increased Epo expression in endometrial carcinomas may be an independent prognostic and/or predictive factor. ..
- Kim S, Rabbani Z, Dewhirst M, Vujaskovic Z, Vollmer R, Schreiber E, et al. Expression of HIF-1alpha, CA IX, VEGF, and MMP-9 in surgically resected non-small cell lung cancer. Lung Cancer. 2005;49:325-35 pubmed..Of the markers considered in this study, CA IX expression status was the most reliable hypoxia marker for predicting tumor aggressiveness. ..
- Fukuda R, Hirota K, Fan F, Jung Y, Ellis L, Semenza G. Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J Biol Chem. 2002;277:38205-11 pubmed..Involvement of the MAP kinase pathway represents a novel mechanism for the induction of HIF-1 alpha protein expression in human cancer cells. ..
- Kondo S, Seo S, Yoshizaki T, Wakisaka N, Furukawa M, Joab I, et al. EBV latent membrane protein 1 up-regulates hypoxia-inducible factor 1alpha through Siah1-mediated down-regulation of prolyl hydroxylases 1 and 3 in nasopharyngeal epithelial cells. Cancer Res. 2006;66:9870-7 pubmedHypoxia-inducible factor 1 (HIF1) is up-regulated in most malignant tumors usually via interruption of ubiquitination and proteasomal degradation of its subunit alpha...
- Semenza G, Wang G. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol. 1992;12:5447-54 pubmed..We have thus defined a functionally tripartite, 50-nt hypoxia-inducible enhancer which binds several nuclear factors, one of which is induced by hypoxia via de novo protein synthesis. ..
- Pereira T, Zheng X, Ruas J, Tanimoto K, Poellinger L. Identification of residues critical for regulation of protein stability and the transactivation function of the hypoxia-inducible factor-1alpha by the von Hippel-Lindau tumor suppressor gene product. J Biol Chem. 2003;278:6816-23 pubmed..In conclusion, we have identified by mutation analysis several residues that are critical for either one or both of the interdigitated and conditionally regulated degradation and transactivation functions of the N-TAD of HIF-1alpha. ..
- Jung J, Kim H, Lee C, Shin Y, Kim Y, Kang G, et al. STAT3 inhibits the degradation of HIF-1alpha by pVHL-mediated ubiquitination. Exp Mol Med. 2008;40:479-85 pubmed..Taken together, our results suggest that STAT3 decreases the pVHL-mediated ubiquitination of HIF-1alpha through competition with pVHL for binding to HIF-1 alpha, and then stabilizes HIF-1alpha protein levels. ..
- Chen C, Chu J, Su W, Huang S, Lee W. Hypoxia and metabolic phenotypes during breast carcinogenesis: expression of HIF-1alpha, GLUT1, and CAIX. Virchows Arch. 2010;457:53-61 pubmed publisher..GLUT1 expression (glycolytic phenotype) and CAIX expression (acid-resistant phenotype) may result in a powerful adaptive advantage and represent an aggressive phenotype. ..
- Kang M, Jung S, Jung J, Kim S, Jung H, Kim T, et al. Associations between single nucleotide polymorphisms of MMP2, VEGF, and HIF1A genes and the risk of developing colorectal cancer. Anticancer Res. 2011;31:575-84 pubmed..There is a significant association between the HIF1A 1772C/T SNP and the risk of developing colorectal cancer, especially in individuals older than 60 years. ..
- Krishnamachary B, Penet M, Nimmagadda S, Mironchik Y, Raman V, Solaiyappan M, et al. Hypoxia regulates CD44 and its variant isoforms through HIF-1? in triple negative breast cancer. PLoS ONE. 2012;7:e44078 pubmed publisher..Data from these cell studies were further supported by in vivo observations that hypoxic tumor regions contained cells with a higher concentration of CD44 expression. ..
- Baracca A, Sgarbi G, Padula A, Solaini G. Glucose plays a main role in human fibroblasts adaptation to hypoxia. Int J Biochem Cell Biol. 2013;45:1356-65 pubmed publisher..Therefore, our data show for the first time that glucose availability significantly affects the hypoxia-induced HIF-1/BNIP3 response, and in particular glucose absence results in enhancing the OXPHOS rate. ..
- Berra E, Benizri E, Ginouves A, Volmat V, Roux D, Pouyssegur J. HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. EMBO J. 2003;22:4082-90 pubmed..Interestingly, PHD2 is upregulated by hypoxia, providing an HIF-1-dependent auto-regulatory mechanism driven by the oxygen tension. ..
- Zheng X, Linke S, Dias J, Zheng X, Gradin K, Wallis T, et al. Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways. Proc Natl Acad Sci U S A. 2008;105:3368-73 pubmed publisher..In conclusion, the data reveal posttranslational modification of the activated form of the Notch receptor and an intricate mode of cross-coupling between the Notch and hypoxia signaling pathways. ..
- Lim J, Lee Y, Chun Y, Chen J, Kim J, Park J. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. Mol Cell. 2010;38:864-78 pubmed publisher..Our results suggest that crosstalk between oxygen- and redox-responsive signal transducers occurs through the SIRT1-HIF-1alpha interaction. ..
- Neal C, Michael M, Rawlings L, Van der Hoek M, Gleadle J. The VHL-dependent regulation of microRNAs in renal cancer. BMC Med. 2010;8:64 pubmed publisher..See Commentary: http://www.biomedcentral.com/1741-7015/8/65. ..
- Higashimura Y, Nakajima Y, Yamaji R, Harada N, Shibasaki F, Nakano Y, et al. Up-regulation of glyceraldehyde-3-phosphate dehydrogenase gene expression by HIF-1 activity depending on Sp1 in hypoxic breast cancer cells. Arch Biochem Biophys. 2011;509:1-8 pubmed publisher..These results indicate that in MCF-7 cells, the activation of HIF-1 on the novel HRE contributes to the breast cancer-specific hypoxic induction of GAPDH gene expression and absolutely depends on the presence of Sp1 on the GC-box. ..
- Carbia Nagashima A, Gerez J, Perez Castro C, Paez Pereda M, Silberstein S, Stalla G, et al. RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia. Cell. 2007;131:309-23 pubmed..Together, these findings point to a central role of RSUME in the regulation of sumoylation and, hence, several critical regulatory pathways in mammalian cells. ..
- Diebold I, Djordjevic T, Hess J, Gorlach A. Rac-1 promotes pulmonary artery smooth muscle cell proliferation by upregulation of plasminogen activator inhibitor-1: role of NFkappaB-dependent hypoxia-inducible factor-1alpha transcription. Thromb Haemost. 2008;100:1021-8 pubmed..These findings indicate that Rac-1 is an important mediator of thrombin signaling and may contribute to pulmonary vascular remodeling via HIF-1-dependent upregulation of PAI-1 leading to enhanced proliferation of PASMC. ..
- Gilkes D, Bajpai S, Chaturvedi P, Wirtz D, Semenza G. Hypoxia-inducible factor 1 (HIF-1) promotes extracellular matrix remodeling under hypoxic conditions by inducing P4HA1, P4HA2, and PLOD2 expression in fibroblasts. J Biol Chem. 2013;288:10819-29 pubmed publisher..HIF-1-dependent ECM remodeling by hypoxic fibroblasts induces changes in breast cancer cell morphology, adhesion, and motility that promote invasion and metastasis...
- Ginouves A, Ilc K, Macías N, Pouyssegur J, Berra E. PHDs overactivation during chronic hypoxia "desensitizes" HIFalpha and protects cells from necrosis. Proc Natl Acad Sci U S A. 2008;105:4745-50 pubmed publisher..However, here we show that chronic hypoxia induces HIF1/2alpha"desensitization" in cellulo and in mice...
- Mole D, Blancher C, Copley R, Pollard P, Gleadle J, Ragoussis J, et al. Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts. J Biol Chem. 2009;284:16767-75 pubmed publisher..Given emerging evidence for biologically distinct functions of HIF-1alpha versus HIF-2alpha understanding the mechanisms restricting HIF-2alpha activity will be of interest. ..
- Nicholas S, Sumbayev V. The role of redox-dependent mechanisms in the downregulation of ligand-induced Toll-like receptors 7, 8 and 4-mediated HIF-1 alpha prolyl hydroxylation. Immunol Cell Biol. 2010;88:180-6 pubmed publisher..In both cases, downregulation of HIF-1 alpha prolyl hydroxylation correlates with a decrease in intracellular iron (II). ..
- Karapetsas A, Giannakakis A, Pavlaki M, Panayiotidis M, Sandaltzopoulos R, Galanis A. Biochemical and molecular analysis of the interaction between ERK2 MAP kinase and hypoxia inducible factor-1?. Int J Biochem Cell Biol. 2011;43:1582-90 pubmed publisher..The identification of an ERK2 recognition domain on HIF-1? opens new avenues for the analysis of HIF-1?-related ERK2 signaling and may allow designing of interfering compounds. ..
- Su K, Tian Y, Wang J, Shi W, Luo D, Liu J, et al. HIF-1? acts downstream of TNF-? to inhibit vasodilator-stimulated phosphoprotein expression and modulates the adhesion and proliferation of breast cancer cells. DNA Cell Biol. 2012;31:1078-87 pubmed publisher..These data provide new insight into the potential anti-tumor effects of TNF-?. ..
- Kamura T, Sato S, Iwai K, Czyzyk Krzeska M, Conaway R, Conaway J. Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex. Proc Natl Acad Sci U S A. 2000;97:10430-5 pubmed..Our findings provide new insight into the function of the VHL tumor suppressor protein, and they provide a foundation for future investigations of the mechanisms underlying VHL regulation of oxygen-dependent gene expression. ..
- Yamamoto Y, Ibusuki M, Okumura Y, Kawasoe T, Kai K, Iyama K, et al. Hypoxia-inducible factor 1alpha is closely linked to an aggressive phenotype in breast cancer. Breast Cancer Res Treat. 2008;110:465-75 pubmed..It may be useful to study the expression of HIF-1alpha using immunohistochemical analysis for better understanding of the tumor characteristics of breast cancer. ..
- Filippi S, Latini P, Frontini M, Palitti F, Egly J, Proietti de Santis L. CSB protein is (a direct target of HIF-1 and) a critical mediator of the hypoxic response. EMBO J. 2008;27:2545-56 pubmed publisher..The outcome of this study provides new insights into the understanding of the molecular basis of the CS phenotype and the involvement of the CSB protein in the hypoxic response pathway. ..
- Sumbayev V, Nicholas S, Streatfield C, Gibbs B. Involvement of hypoxia-inducible factor-1 HiF(1alpha) in IgE-mediated primary human basophil responses. Eur J Immunol. 2009;39:3511-9 pubmed publisher..In addition, HIF-1alpha protein alters IgE-induced ATP depletion in basophils, thus also supporting the production of the pro-allergic cytokine IL-4. ..
- Keely S, Glover L, Weissmueller T, MacManus C, Fillon S, Fennimore B, et al. Hypoxia-inducible factor-dependent regulation of platelet-activating factor receptor as a route for gram-positive bacterial translocation across epithelia. Mol Biol Cell. 2010;21:538-46 pubmed publisher..Together, these findings reveal that some strains of Gram-positive bacteria exploit HIF-regulated PAFr as a means for translocation through intestinal epithelial cells. ..
- Ghosh G, Subramanian I, Adhikari N, Zhang X, Joshi H, Basi D, et al. Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-? isoforms and promotes angiogenesis. J Clin Invest. 2010;120:4141-54 pubmed publisher..These results suggest that miR-322/424 plays an important physiological role in post-ischemic vascular remodeling and angiogenesis. ..
- Altun M, Zhao B, Velasco K, Liu H, Hassink G, Paschke J, et al. Ubiquitin-specific protease 19 (USP19) regulates hypoxia-inducible factor 1? (HIF-1?) during hypoxia. J Biol Chem. 2012;287:1962-9 pubmed publisher..In the absence of USP19, cells fail to mount an appropriate response to hypoxia, indicating an important role for this enzyme in normal or pathological conditions. ..
- Yoo Y, Oh S, Park E, Cho H, Lee N, Park H, et al. Hepatitis B virus X protein enhances transcriptional activity of hypoxia-inducible factor-1alpha through activation of mitogen-activated protein kinase pathway. J Biol Chem. 2003;278:39076-84 pubmed
- Peng X, Karna P, Cao Z, Jiang B, Zhou M, Yang L. Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J Biol Chem. 2006;281:25903-14 pubmed..Understanding key molecular events in EGFR signaling-induced apoptosis resistance should provide new information for the development of novel therapeutic agents targeting EGFR, HIF-1alpha, and/or survivin. ..
- Polosukhin V, Lawson W, Milstone A, Egunova S, Kulipanov A, Tchuvakin S, et al. Association of progressive structural changes in the bronchial epithelium with subepithelial fibrous remodeling: a potential role for hypoxia. Virchows Arch. 2007;451:793-803 pubmed..These findings suggest that the HIF-1alpha pathway is activated in response to subepithelial remodeling and contributes to progressive premalignant epithelial lesions in the airways of tobacco smokers with chronic airway inflammation. ..
- Sutter C, Laughner E, Semenza G. Hypoxia-inducible factor 1alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations. Proc Natl Acad Sci U S A. 2000;97:4748-53 pubmed..We demonstrate that hypoxia results in decreased ubiquitination of HIF-1alpha and that missense mutations increase HIF-1alpha expression under nonhypoxic conditions by blocking ubiquitination. ..
- Generali D, Berruti A, Brizzi M, Campo L, Bonardi S, Wigfield S, et al. Hypoxia-inducible factor-1alpha expression predicts a poor response to primary chemoendocrine therapy and disease-free survival in primary human breast cancer. Clin Cancer Res. 2006;12:4562-8 pubmed
- Chachami G, Paraskeva E, Mingot J, Braliou G, Gorlich D, Simos G. Transport of hypoxia-inducible factor HIF-1alpha into the nucleus involves importins 4 and 7. Biochem Biophys Res Commun. 2009;390:235-40 pubmed publisher..Taken together, our data show that shuttling of HIF-1alpha between cytoplasm and nucleus is a complex process involving several members of the nuclear transport receptor family. ..
- Huerta Yepez S, Baay Guzman G, Bebenek I, Hernandez Pando R, Vega M, Chi L, et al. Hypoxia inducible factor promotes murine allergic airway inflammation and is increased in asthma and rhinitis. Allergy. 2011;66:909-18 pubmed publisher..This study sets out to investigate whether hypoxia-inducible factor (HIF) is essential for development of allergic airway inflammation (AAI) and therefore a potential novel target for asthma treatment...
- Harada H, Inoue M, Itasaka S, Hirota K, Morinibu A, Shinomiya K, et al. Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels. Nat Commun. 2012;3:783 pubmed publisher..For the first time, our data unveil the HIF-1-dependent cellular dynamics during post-irradiation tumour recurrence and provide a rational basis for targeting HIF-1 after radiation therapy. ..
- Thrash Bingham C, Tartof K. aHIF: a natural antisense transcript overexpressed in human renal cancer and during hypoxia. J Natl Cancer Inst. 1999;91:143-51 pubmed..To our knowledge, this is the first case of overexpression of a natural antisense transcript exclusively associated with a specific human malignant disease. ..
- Maranchie J, Vasselli J, Riss J, Bonifacino J, Linehan W, Klausner R. The contribution of VHL substrate binding and HIF1-alpha to the phenotype of VHL loss in renal cell carcinoma. Cancer Cell. 2002;1:247-55 pubmed..We further demonstrate that normoxic stabilization of HIF1alpha alone, while capable of mimicking some aspects of VHL loss, is not sufficient to reproduce tumorigenesis, indicating that it is not the critical oncogenic substrate of VHL. ..
- Arnesen T, Kong X, Evjenth R, Gromyko D, Varhaug J, Lin Z, et al. Interaction between HIF-1 alpha (ODD) and hARD1 does not induce acetylation and destabilization of HIF-1 alpha. FEBS Lett. 2005;579:6428-32 pubmed..Moreover, hARD1 does not acetylate and destabilize HIF-1 alpha. However, we find that hARD1 specifically binds HIF-1 alpha, suggesting a putative, still unclear, connection between these proteins. ..
- Trastour C, Benizri E, Ettore F, Ramaioli A, Chamorey E, Pouyssegur J, et al. HIF-1alpha and CA IX staining in invasive breast carcinomas: prognosis and treatment outcome. Int J Cancer. 2007;120:1451-8 pubmed..CA IX is, however, a weaker prognostic and predictive factor than HIF-1alpha, and its association with HIF-1alpha does not modify the survival curve neither response to therapy, compared to HIF-1alpha alone. ..
- Koh M, Darnay B, Powis G. Hypoxia-associated factor, a novel E3-ubiquitin ligase, binds and ubiquitinates hypoxia-inducible factor 1alpha, leading to its oxygen-independent degradation. Mol Cell Biol. 2008;28:7081-95 pubmed publisher..Therefore, HAF is the key mediator of a new HIF-1alpha-specific degradation pathway that degrades HIF-1alpha through a new, oxygen-independent mechanism. ..
- Kenneth N, Mudie S, van Uden P, Rocha S. SWI/SNF regulates the cellular response to hypoxia. J Biol Chem. 2009;284:4123-31 pubmed publisher..These results reveal a previously uncharacterized dependence of hypoxia signaling on the SWI/SNF complex and demonstrate a new level of control over the hypoxia-inducible factor-1alpha system. ..
- Moin S, Chandra V, Arya R, Jameel S. The hepatitis E virus ORF3 protein stabilizes HIF-1alpha and enhances HIF-1-mediated transcriptional activity through p300/CBP. Cell Microbiol. 2009;11:1409-21 pubmed publisher..Our results reveal a two-pronged strategy through which the ORF3 protein might modulate the energy homeostasis in HEV infected cells and thus contribute to pathogenesis. ..
- Arjamaa O, Nikinmaa M, Salminen A, Kaarniranta K. Regulatory role of HIF-1alpha in the pathogenesis of age-related macular degeneration (AMD). Ageing Res Rev. 2009;8:349-58 pubmed publisher..In this review, we discuss role of HIF in AMD pathology and as a possible therapeutic target. ..
- Kuo H, Lee D, Xia W, Wei Y, Hung M. TNFalpha induces HIF-1alpha expression through activation of IKKbeta. Biochem Biophys Res Commun. 2009;389:640-4 pubmed publisher..Our findings indicate that TNFalpha-induced HIF-1alpha accumulation is IKKbeta dependent, and may enable further understanding of the HIF-1alpha regulation by inflammatory signals. ..
- Kallergi G, Markomanolaki H, Giannoukaraki V, Papadaki M, Strati A, Lianidou E, et al. Hypoxia-inducible factor-1alpha and vascular endothelial growth factor expression in circulating tumor cells of breast cancer patients. Breast Cancer Res. 2009;11:R84 pubmed publisher..The expression of pFAK, HIF-1alpha, VEGF and VEGF2 in CTCs of patients with metastatic breast cancer could explain the metastatic potential of these cells and may provide a therapeutic target for their elimination. ..
- Gradin K, McGuire J, Wenger R, Kvietikova I, fhitelaw M, Toftgard R, et al. Functional interference between hypoxia and dioxin signal transduction pathways: competition for recruitment of the Arnt transcription factor. Mol Cell Biol. 1996;16:5221-31 pubmed..Given the critical role of hsp90 for ligand binding activity and activation of the dioxin receptor, it is therefore possible that HIF-1 alpha is regulated by a similar mechanism, possibly by binding an as yet unknown class of ligands. ..
- Sivridis E, Giatromanolaki A, Gatter K, Harris A, Koukourakis M. Association of hypoxia-inducible factors 1alpha and 2alpha with activated angiogenic pathways and prognosis in patients with endometrial carcinoma. Cancer. 2002;95:1055-63 pubmed..HIF-2alpha accumulation is associated with increased expression of the angiogenic factor TP. ..
- Maynard M, Qi H, Chung J, Lee E, Kondo Y, Hara S, et al. Multiple splice variants of the human HIF-3 alpha locus are targets of the von Hippel-Lindau E3 ubiquitin ligase complex. J Biol Chem. 2003;278:11032-40 pubmed..These results demonstrate additional targets of the pVHL complex and suggest a growing complexity in the regulation of hypoxia-inducible genes by the HIF family of transcription factors. ..
- Hu C, Wang L, Chodosh L, Keith B, Simon M. Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol Cell Biol. 2003;23:9361-74 pubmed..Importantly, HIF-1alpha (and not HIF-2alpha) stimulates glycolytic gene expression in both types of cells, clearly showing for the first time that HIF-1alpha and HIF-2alpha have unique targets. ..
- Kilic M, Kasperczyk H, Fulda S, Debatin K. Role of hypoxia inducible factor-1 alpha in modulation of apoptosis resistance. Oncogene. 2007;26:2027-38 pubmed..Thus, hypoxia-inducible genes may represent novel targets for therapeutic intervention in some pediatric tumors, which warrants further investigation. ..
- DeClerck K, Elble R. The role of hypoxia and acidosis in promoting metastasis and resistance to chemotherapy. Front Biosci (Landmark Ed). 2010;15:213-25 pubmed..The ability to target the hypoxic compartment should allow longer progression-free survival and overall survival of patients bearing solid tumor malignancies. ..
- Werth N, Beerlage C, Rosenberger C, Yazdi A, Edelmann M, Amr A, et al. Activation of hypoxia inducible factor 1 is a general phenomenon in infections with human pathogens. PLoS ONE. 2010;5:e11576 pubmed publisher..Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections. ..
- Wang X, Liu Y, Ren H, Yuan Z, Li S, Sheng J, et al. Polymorphisms in the hypoxia-inducible factor-1α gene confer susceptibility to pancreatic cancer. Cancer Biol Ther. 2011;12:383-7 pubmed..In conclusion, the C1772T and G1790A SNPs in the HIF-1α gene increase the susceptibility to pancreatic cancer. In addition, the G1790A SNP is associated with increases in tumor-produced HIF-1α and in the progression of the cancer. ..
- Yasuo M, Mizuno S, Kraskauskas D, Bogaard H, Natarajan R, Cool C, et al. Hypoxia inducible factor-1? in human emphysema lung tissue. Eur Respir J. 2011;37:775-83 pubmed publisher..In conclusion, reduced expression of HIF-1? protein in severe COPD is consistent with the concept of a lung structure maintenance programme which is impaired on a molecular level...
- Majmundar A, Wong W, Simon M. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 2010;40:294-309 pubmed publisher..enzymes (PHDs), the HIF? subunits are intricately responsive to numerous other factors, including factor-inhibiting HIF1? (FIH1), sirtuins, and metabolites...