HIF-1 alpha

Summary

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
Species: human
Products:     HIF-1 alpha

Top Publications

  1. Kolyada A, Tighiouart H, Perianayagam M, Liangos O, Madias N, Jaber B. A genetic variant of hypoxia-inducible factor-1alpha is associated with adverse outcomes in acute kidney injury. Kidney Int. 2009;75:1322-1329 pubmed publisher
    ..Despite the limited cohort size, our study found this particular HIF-1alpha genetic variant to be associated with disease severity and adverse outcomes in AKI. Larger studies are needed to confirm these relationships. ..
  2. Luo W, Zhong J, Chang R, Hu H, Pandey A, Semenza G. Hsp70 and CHIP selectively mediate ubiquitination and degradation of hypoxia-inducible factor (HIF)-1alpha but Not HIF-2alpha. J Biol Chem. 2010;285:3651-63 pubmed publisher
    ..Thus, Hsp70- and CHIP-dependent ubiquitination represents a molecular mechanism by which prolonged hypoxia selectively reduces the levels of HIF-1alpha but not HIF-2alpha protein. ..
  3. Mowat F, Luhmann U, Smith A, Lange C, Duran Y, Harten S, et al. HIF-1alpha and HIF-2alpha are differentially activated in distinct cell populations in retinal ischaemia. PLoS ONE. 2010;5:e11103 pubmed publisher
    ..Our findings suggest that HIF-2alpha activation plays a key role in regulating the response of Müller glia to hypoxia. ..
  4. Trisciuoglio D, Gabellini C, Desideri M, Ziparo E, Zupi G, Del Bufalo D. Bcl-2 regulates HIF-1alpha protein stabilization in hypoxic melanoma cells via the molecular chaperone HSP90. PLoS ONE. 2010;5:e11772 pubmed publisher
    ..We identified the stabilization of HIF-1alpha protein as a mechanism through which bcl-2 induces the activation of HIF-1 in hypoxic tumour cells involving the beta isoform of molecular chaperone HSP90. ..
  5. Jiang B, Rue E, Wang G, Roe R, Semenza G. Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J Biol Chem. 1996;271:17771-8 pubmed
    ..Overexpression of a HIF-1alpha construct with deletions of the basic domain and carboxy terminus blocked reporter gene activation by endogenous HIF-1 in hypoxic cells. ..
  6. Cai Q, Murakami M, Si H, Robertson E. A potential alpha-helix motif in the amino terminus of LANA encoded by Kaposi's sarcoma-associated herpesvirus is critical for nuclear accumulation of HIF-1alpha in normoxia. J Virol. 2007;81:10413-23 pubmed
    ..Therefore, these data show that LANA can function not only as an inhibitor of HIF-1alpha suppressor proteins but can also induce nuclear accumulation of HIF-1alpha during KSHV latent infection. ..
  7. Shin D, Li S, Yang S, Lee B, Lee M, Park J. Inhibitor of nuclear factor-kappaB alpha derepresses hypoxia-inducible factor-1 during moderate hypoxia by sequestering factor inhibiting hypoxia-inducible factor from hypoxia-inducible factor 1alpha. FEBS J. 2009;276:3470-80 pubmed publisher
    ..Therefore, IkappaB alpha, owing to its interactions with NF-kappaB and HIF-1alpha, may play a pivotal role in the crosstalk between the molecular events that underlie inflammatory and hypoxic responses. ..
  8. Krieg A, Rankin E, Chan D, Razorenova O, Fernandez S, Giaccia A. Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth. Mol Cell Biol. 2010;30:344-53 pubmed publisher
    ..Thus, hypoxic regulation of JMJD1A acts as a signal amplifier to facilitate hypoxic gene expression, ultimately enhancing tumor growth. ..
  9. Cao D, Hou M, Guan Y, Jiang M, Yang Y, Gou H. Expression of HIF-1alpha and VEGF in colorectal cancer: association with clinical outcomes and prognostic implications. BMC Cancer. 2009;9:432 pubmed publisher
    ..Treatment that inhibits HIF-1alpha might be a promising targeted approach in CRC to exhibit its potential to improve outcomes in future perspective, just as VEGF targeting has proved to be. ..

More Information

Publications424 found, 100 shown here

  1. Dong Z, Yao D, Li S, Li Y, Tai B, Qiu L, et al. [Expression characteristics of hypoxia inducible factor-1a and its clinical values in hepatocellular carcinoma]. Zhonghua Gan Zang Bing Za Zhi. 2010;18:506-10 pubmed publisher
    ..No correlation was found between HIF-1alpha and tumor numbers or positive-HBsAg. HIF-1alpha expression is associated with occurrence and development of HCC, and is perhaps a target molecule for HCC therapy. ..
  2. Newton I, Kenneth N, Appleton P, Näthke I, Rocha S. Adenomatous polyposis coli and hypoxia-inducible factor-1{alpha} have an antagonistic connection. Mol Biol Cell. 2010;21:3630-8 pubmed publisher
    ..These results reveal down-regulation of APC as a new mechanism that contributes to the survival advantage induced by hypoxia and also show that loss of APC mutations produces a survival advantage by mimicking hypoxic conditions. ..
  3. Du J, Xu R, Hu Z, Tian Y, Zhu Y, Gu L, et al. PI3K and ERK-induced Rac1 activation mediates hypoxia-induced HIF-1? expression in MCF-7 breast cancer cells. PLoS ONE. 2011;6:e25213 pubmed publisher
    ..Taken together, our study demonstrated that hypoxia-induced HIF-1? expression involves a cascade of signaling events including ROS generation, activation of PI3K and ERK signaling, and subsequent activation of Rac1. ..
  4. Ohh M, Park C, Ivan M, Hoffman M, Kim T, Huang L, et al. Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol. 2000;2:423-7 pubmed
    ..These results strengthen the link between overaccumulation of HIF and development of VHL disease. ..
  5. Berra E, Richard D, Gothié E, Pouyssegur J. HIF-1-dependent transcriptional activity is required for oxygen-mediated HIF-1alpha degradation. FEBS Lett. 2001;491:85-90 pubmed
    ..Although HPTF is not yet molecularly identified, it is clearly distinct from the von Hippel-Lindau protein (pVHL). ..
  6. Pipinikas C, Carter N, Corbishley C, Fenske C. HIF-1alpha mRNA gene expression levels in improved diagnosis of early stages of prostate cancer. Biomarkers. 2008;13:680-91 pubmed
  7. Zhang P, Zhang X, Hao X, Wang Y, Hui Y, Wang H, et al. Rac1 activates HIF-1 in retinal pigment epithelium cells under hypoxia. Graefes Arch Clin Exp Ophthalmol. 2009;247:633-9 pubmed publisher
    ..Rac1 is crucial to activate HIF-1 in RPE cells under hypoxia, which may be a novel target other than VEGF and HIF-1 in developing CNV inhibitors. ..
  8. Moroz E, Carlin S, Dyomina K, Burke S, Thaler H, Blasberg R, et al. Real-time imaging of HIF-1alpha stabilization and degradation. PLoS ONE. 2009;4:e5077 pubmed publisher
    ..Overall, the continuous bioluminescence readout of HIF-1alpha/FLuc stabilization in vitro and in vivo will facilitate the development and validation of therapeutics that affect the stability and accumulation of HIF-1alpha. ..
  9. Yan M, Rayoo M, Takano E, Thorne H, Fox S. BRCA1 tumours correlate with a HIF-1alpha phenotype and have a poor prognosis through modulation of hydroxylase enzyme profile expression. Br J Cancer. 2009;101:1168-74 pubmed publisher
    ..This may have important implications, as these tumours may respond to compounds directed against HIF-1alpha or its downstream targets. ..
  10. Cheng J, Klausen C, Leung P. Hypoxia-inducible factor 1 alpha mediates epidermal growth factor-induced down-regulation of E-cadherin expression and cell invasion in human ovarian cancer cells. Cancer Lett. 2013;329:197-206 pubmed publisher
    ..This study demonstrates an important role for HIF-1? in mediating the effects of EGF on Snail, Slug and E-cadherin expression as well as invasiveness in human ovarian cancer cells. ..
  11. Ietta F, Wu Y, Winter J, Xu J, Wang J, Post M, et al. Dynamic HIF1A regulation during human placental development. Biol Reprod. 2006;75:112-21 pubmed
    ..These data demonstrate that during placental development, HIF1A is regulated by temporal and spatial changes in expression and association of molecules forming the multi-protein VHLCBC complex as well as prolyl hydroxylase activities. ..
  12. Kong X, Alvarez Castelao B, Lin Z, Castaño J, Caro J. Constitutive/hypoxic degradation of HIF-alpha proteins by the proteasome is independent of von Hippel Lindau protein ubiquitylation and the transactivation activity of the protein. J Biol Chem. 2007;282:15498-505 pubmed
  13. Surazynski A, Donald S, Cooper S, Whiteside M, Salnikow K, Liu Y, et al. Extracellular matrix and HIF-1 signaling: the role of prolidase. Int J Cancer. 2008;122:1435-40 pubmed
    ..These findings show that metabolism of imidodipeptides by prolidase plays a previously unrecognized role in angiogenic signaling. ..
  14. Jacobs E, Hsing A, Bain E, Stevens V, Wang Y, Chen J, et al. Polymorphisms in angiogenesis-related genes and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2008;17:972-7 pubmed publisher
    ..None of the SNPs examined seem likely to be importantly associated with risk of overall or advanced prostate cancer. ..
  15. Lall H, Coughlan K, Sumbayev V. HIF-1alpha protein is an essential factor for protection of myeloid cells against LPS-induced depletion of ATP and apoptosis that supports Toll-like receptor 4-mediated production of IL-6. Mol Immunol. 2008;45:3045-9 pubmed publisher
    ..On the other hand HIF-1alpha protein is selectively required for down-regulation of ASK1 activated during LPS-induced TLR4 downstream signalling. ..
  16. Diebold I, Petry A, Djordjevic T, BelAiba R, Fineman J, Black S, et al. Reciprocal regulation of Rac1 and PAK-1 by HIF-1alpha: a positive-feedback loop promoting pulmonary vascular remodeling. Antioxid Redox Signal. 2010;13:399-412 pubmed publisher
  17. Xu Z, Chen X, Niu J, Liu E, Li C, Peng C. [The prognostic significance of Omi/HtrA2 expression, and correlation between Omi/HtrA2 and hypoxia-inducible factor-1? in primary hepatocellular carcinoma cells]. Zhonghua Wai Ke Za Zhi. 2012;50:49-52 pubmed
    ..During the apoptotic process Omi/HtrA2 participating in hepatocellular carcinoma cells, HIF-1? is involved in the controlling and regulating of Omi/HtrA2 expression. ..
  18. Mottet D, Michel G, Renard P, Ninane N, Raes M, Michiels C. ERK and calcium in activation of HIF-1. Ann N Y Acad Sci. 2002;973:448-53 pubmed
    ..Altogether, these results suggest that calcium and calmodulin would act upstream of ERK in the hypoxia signal transduction pathway leading to enhanced HIF-1 transcriptional activity. ..
  19. Zhou J, Schmid T, Brüne B. Tumor necrosis factor-alpha causes accumulation of a ubiquitinated form of hypoxia inducible factor-1alpha through a nuclear factor-kappaB-dependent pathway. Mol Biol Cell. 2003;14:2216-25 pubmed
    ..These data indicate that HIF-1alpha accumulation by TNF-alpha demands the NF-kappaB pathway, preserves ubiquitination of HIF-1alpha, and allows the HIF-1alpha-pVHL interaction. ..
  20. Corn P, McDonald E, Herman J, El Deiry W. Tat-binding protein-1, a component of the 26S proteasome, contributes to the E3 ubiquitin ligase function of the von Hippel-Lindau protein. Nat Genet. 2003;35:229-37 pubmed
    ..pVHL functions in a multi-subunit E3 ubiquitin ligase that targets the hypoxia-inducible transcription factor Hif1 alpha for proteasomal degradation during normoxia...
  21. Beyer S, Kristensen M, Jensen K, Johansen J, Staller P. The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF. J Biol Chem. 2008;283:36542-52 pubmed publisher
    ..Studies on ectopically expressed JMJD1A and JMJD2B indicate that both proteins retain their histone lysine demethylase activity in hypoxia and thereby might impact the hypoxic gene expression program. ..
  22. Gordan J, Lal P, Dondeti V, Letrero R, Parekh K, Oquendo C, et al. HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell. 2008;14:435-46 pubmed publisher
    ..These reproducible distinctions in ccRCC behavior delineate HIF-alpha effects on c-Myc in vivo and suggest molecular criteria for selecting targeted therapies. ..
  23. Li K, Zhang Y, Dan Z, Wang Y, Ren Z. Association of the hypoxia inducible factor-1alpha gene polymorphisms with gastric cancer in Tibetans. Biochem Genet. 2009;47:625-34 pubmed publisher
    ..As for the C1772T polymorphism, no positive correlation was found between gastric cancer patients and controls (P = 0.06). Our results suggest that the HIF-1alpha G1790A polymorphism may be associated with gastric cancer in Tibetans. ..
  24. Park J, Lee J, Shin D, Jang K, Kim H, Kong G. Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1? mediated by the PTEN/PI3K/Akt pathway. Oncogene. 2011;30:4578-89 pubmed publisher
  25. Luo W, Hu H, Chang R, Zhong J, Knabel M, O Meally R, et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell. 2011;145:732-44 pubmed publisher
    ..Thus, PKM2 participates in a positive feedback loop that promotes HIF-1 transactivation and reprograms glucose metabolism in cancer cells. ..
  26. Xia L, Mo P, Huang W, Zhang L, Wang Y, Zhu H, et al. The TNF-?/ROS/HIF-1-induced upregulation of FoxMI expression promotes HCC proliferation and resistance to apoptosis. Carcinogenesis. 2012;33:2250-9 pubmed publisher
    ..revealed that the induction of FoxM1 expression by TNF-? was dependent upon the hypoxia-inducible factor 1 (HIF1)-1 and HIF1-3/4 binding sites within the FoxM1 promoter...
  27. Sato Tadano A, Suzuki T, Amari M, Takagi K, Miki Y, Tamaki K, et al. Hexokinase II in breast carcinoma: a potent prognostic factor associated with hypoxia-inducible factor-1? and Ki-67. Cancer Sci. 2013;104:1380-8 pubmed publisher
    ..The status of HKII is therefore considered a potent prognostic factor in human breast cancer patients. ..
  28. Zhang Z, Zhang Q, Wang X, Tian J. Hypoxia-inducible factor 1 alpha (HIF-1α) as a prognostic indicator in patients with gastric tumors: a meta-analysis. Asian Pac J Cancer Prev. 2013;14:4195-8 pubmed
    ..67, 95%CI: 0.99-2.82; P=0.06). HIF-1α was associated with poor OS, but not DFS, especially for Asian patients. But studies evaluating relationships of HIF- 1α with OS and DFS in non-Asian gastric cancer patients appear needed. ..
  29. Min J, Yang H, Ivan M, Gertler F, Kaelin W, Pavletich N. Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling. Science. 2002;296:1886-9 pubmed
    ..Although the beta sheet-like interactions contribute to the stability of the complex, the hydroxyproline contacts are central to the strict specificity characteristic of signaling. ..
  30. Jeong J, Bae M, Ahn M, Kim S, Sohn T, Bae M, et al. Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. Cell. 2002;111:709-20 pubmed
    ..Therefore, we have concluded that the role of ARD1 in the acetylation of HIF-1alpha provides a key regulatory mechanism underlying HIF-1alpha stability. ..
  31. Huang S, Wu M, Shun C, Wang H, Hsieh C, Kuo M, et al. Cyclooxygenase-2 increases hypoxia-inducible factor-1 and vascular endothelial growth factor to promote angiogenesis in gastric carcinoma. J Biomed Sci. 2005;12:229-41 pubmed
    ..Our work supports the COX-2/PGE2/HIF-1alpha/VEGF pathway possibly contributing to tumor angiogenesis in GC. ..
  32. Fransen K, Fenech M, Fredrikson M, Dabrosin C, Söderkvist P. Association between ulcerative growth and hypoxia inducible factor-1alpha polymorphisms in colorectal cancer patients. Mol Carcinog. 2006;45:833-40 pubmed
    ..Future screening of the polymorphic HIF-1alpha allele may therefore be of importance in the selection of treatment strategies of CRC. ..
  33. Koda M, Sulkowska M, Wincewicz A, Kanczuga Koda L, Musiatowicz B, Szymanska M, et al. Expression of leptin, leptin receptor, and hypoxia-inducible factor 1 alpha in human endometrial cancer. Ann N Y Acad Sci. 2007;1095:90-8 pubmed
    ..Ob could exert autocrine effect to stimulate endometrial cancer progression. Thus the autocrine Ob loop should be taken into consideration as a novel potential target in endometrial cancer prevention and treatment. ..
  34. Ma J, Zhang L, Ru G, Zhao Z, Xu W. Upregulation of hypoxia inducible factor 1alpha mRNA is associated with elevated vascular endothelial growth factor expression and excessive angiogenesis and predicts a poor prognosis in gastric carcinoma. World J Gastroenterol. 2007;13:1680-6 pubmed
    ..HIF-1alpha may induce the angiogenesis in gastric carcinoma by upregulating the transcription of VEGF gene, and take part in tumor invasion and metastasis. They can be used as prognostic markers of gastric cancer in clinical practice. ..
  35. Tuttle S, Maity A, Oprysko P, Kachur A, Ayene I, Biaglow J, et al. Detection of reactive oxygen species via endogenous oxidative pentose phosphate cycle activity in response to oxygen concentration: implications for the mechanism of HIF-1alpha stabilization under moderate hypoxia. J Biol Chem. 2007;282:36790-6 pubmed
    ..Therefore, we conclude that the oxygen dependence of the prolyl hydroxylase reaction is sufficient to mediate HIF-1alpha stability under moderate as well as severe hypoxia. ..
  36. André H, Pereira T. Identification of an alternative mechanism of degradation of the hypoxia-inducible factor-1alpha. J Biol Chem. 2008;283:29375-84 pubmed publisher
    ..In conclusion, we show the first evidence of a novel mechanism of degradation of HIF-1alpha at normoxia that involves pVHL but is not mediated by PHDs 1-3 or by degradation boxes surrounding Pro(402) and Pro(563). ..
  37. Morote Garcia J, Rosenberger P, Nivillac N, Coe I, Eltzschig H. Hypoxia-inducible factor-dependent repression of equilibrative nucleoside transporter 2 attenuates mucosal inflammation during intestinal hypoxia. Gastroenterology. 2009;136:607-18 pubmed publisher
    ..HIF-1alpha-dependent repression of ENT2 increases mucosal adenosine signaling and attenuates hypoxia-associated inflammation of the intestine. ..
  38. Nardinocchi L, Puca R, Sacchi A, D Orazi G. Inhibition of HIF-1alpha activity by homeodomain-interacting protein kinase-2 correlates with sensitization of chemoresistant cells to undergo apoptosis. Mol Cancer. 2009;8:1 pubmed publisher
    ..Thus potential use of HIPK2 is promising for cancer treatment by potentiating cytotoxic therapies, regardless of p53 cell status. ..
  39. Nakamura J, Kitajima Y, Kai K, Mitsuno M, Ide T, Hashiguchi K, et al. Hypoxia-inducible factor-1alpha expression predicts the response to 5-fluorouracil-based adjuvant chemotherapy in advanced gastric cancer. Oncol Rep. 2009;22:693-9 pubmed
    ..In conclusion, the assessment of the HIF-1alpha expression in the resected tissues might predict the drug response to adjuvant 5-FU chemotherapy in advanced gastric cancer patients. ..
  40. Chen J, Li T, Liu Q, Jiao H, Yang W, Liu X, et al. Clinical and prognostic significance of HIF-1?, PTEN, CD44v6, and survivin for gastric cancer: a meta-analysis. PLoS ONE. 2014;9:e91842 pubmed publisher
    ..The development of strategies against this subset of proteins could lead to new therapeutic approaches. ..
  41. Lando D, Peet D, Whelan D, Gorman J, Whitelaw M. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science. 2002;295:858-61 pubmed
    ..Full induction of HIF-1alpha and -2alpha, therefore, relies on the abrogation of both Pro and Asn hydroxylation, which during normoxia occur at the degradation and COOH-terminal transactivation domains, respectively. ..
  42. Chen D, Li M, Luo J, Gu W. Direct interactions between HIF-1 alpha and Mdm2 modulate p53 function. J Biol Chem. 2003;278:13595-8 pubmed
    ..These results have significant implications regarding the molecular mechanism by which p53 is activated by HIF-1 alpha in response to hypoxia. ..
  43. Linke S, Stojkoski C, Kewley R, Booker G, Whitelaw M, Peet D. Substrate requirements of the oxygen-sensing asparaginyl hydroxylase factor-inhibiting hypoxia-inducible factor. J Biol Chem. 2004;279:14391-7 pubmed
  44. Depping R, Hägele S, Wagner K, Wiesner R, Camenisch G, Wenger R, et al. A dominant-negative isoform of hypoxia-inducible factor-1 alpha specifically expressed in human testis. Biol Reprod. 2004;71:331-9 pubmed
  45. Gillespie D, Whang K, Ragel B, Flynn J, Kelly D, Jensen R. Silencing of hypoxia inducible factor-1alpha by RNA interference attenuates human glioma cell growth in vivo. Clin Cancer Res. 2007;13:2441-8 pubmed
    ..Tumor volume in these siRNA injection experiments was reduced by 50% over the negative controls. These results indicate that transient RNAi directed against HIF-1alpha can effectively curb glioma growth in vivo. ..
  46. Rupp J, Gieffers J, Klinger M, van Zandbergen G, Wrase R, Maass M, et al. Chlamydia pneumoniae directly interferes with HIF-1alpha stabilization in human host cells. Cell Microbiol. 2007;9:2181-91 pubmed
    ..Direct interference with HIF-1alpha stabilization was essential for efficient C. pneumoniae replication in hypoxia and highlights a novel strategy of adaptive pathogen-host interaction in chlamydial diseases. ..
  47. Lyberopoulou A, Venieris E, Mylonis I, Chachami G, Pappas I, Simos G, et al. MgcRacGAP interacts with HIF-1alpha and regulates its transcriptional activity. Cell Physiol Biochem. 2007;20:995-1006 pubmed
    ..Moreover, this inhibition is dependent on the MgcRacGAP domain that interacts with HIF-1alpha. In conclusion, our findings demonstrate that HIF-1alpha function is negatively affected by its interaction with MgcRacGAP. ..
  48. Han Z, Ren H, Zhao H, Chi Y, Chen K, Zhou B, et al. Hypoxia-inducible factor (HIF)-1 alpha directly enhances the transcriptional activity of stem cell factor (SCF) in response to hypoxia and epidermal growth factor (EGF). Carcinogenesis. 2008;29:1853-61 pubmed publisher
    ..Hypoxia and epidermal growth factor receptor signal coexisted in the tumor microenvironment and might promote angiogenesis through HIF-1 alpha-mediated upregulation of SCF and other angiogenic factors. ..
  49. Mera Menéndez F, Hinojar Gutierrez A, Guijarro Rojas M, de Gregorio J, Mera Menéndez E, Sanchez J, et al. Polymorphisms in HIF-1alpha affect presence of lymph node metastasis and can influence tumor size in squamous-cell carcinoma of the glottic larynx. Clin Transl Oncol. 2013;15:358-63 pubmed publisher
    ..006 and p = 0.032). The presence of the TT and GA variants were associated with lymph node metastasis, while the presence of the TT variant can be associated with larger tumor size. ..
  50. Guo M, Cai C, Zhao G, Qiu X, Zhao H, Ma Q, et al. Hypoxia promotes migration and induces CXCR4 expression via HIF-1? activation in human osteosarcoma. PLoS ONE. 2014;9:e90518 pubmed publisher
    ..The hypoxia-HIF-1?-CXCR4 pathway plays a crucial role during the migration of human osteosarcoma cells, and targeting this pathway might represent a novel therapeutic strategy for patients suffering from osteosarcoma. ..
  51. Semenza G, Rue E, Iyer N, Pang M, Kearns W. Assignment of the hypoxia-inducible factor 1alpha gene to a region of conserved synteny on mouse chromosome 12 and human chromosome 14q. Genomics. 1996;34:437-9 pubmed
    ..33. ..
  52. Cho S, Choi Y, Kim J, Jeong S, Kim J, Kim S, et al. Binding and regulation of HIF-1alpha by a subunit of the proteasome complex, PSMA7. FEBS Lett. 2001;498:62-6 pubmed
    ..PSMA7 inhibited the transactivation function of HIF-1alpha under both normoxic and hypoxia-mimicking conditions. In addition, we show that the PSMA7-mediated regulation of HIF-1alpha activity is associated with the proteasome pathway. ..
  53. Grosfeld A, Andre J, Hauguel De Mouzon S, Berra E, Pouyssegur J, Guerre Millo M. Hypoxia-inducible factor 1 transactivates the human leptin gene promoter. J Biol Chem. 2002;277:42953-7 pubmed
    ..These data demonstrate that leptin is a new hypoxia-inducible gene, which is stimulated in a placental cell line through HIF-1 interaction with a consensus HRE site located at -116 in the proximal promoter. ..
  54. Nishi H, Nakada T, Hokamura M, Osakabe Y, Itokazu O, Huang L, et al. Hypoxia-inducible factor-1 transactivates transforming growth factor-beta3 in trophoblast. Endocrinology. 2004;145:4113-8 pubmed
    ..Our results provide evidence that regulation of TGF-beta3 promoter activity by HIF-1 represents a mechanism for trophoblast differentiation during hypoxia. ..
  55. Tuckerman J, Zhao Y, Hewitson K, Tian Y, Pugh C, Ratcliffe P, et al. Determination and comparison of specific activity of the HIF-prolyl hydroxylases. FEBS Lett. 2004;576:145-50 pubmed
  56. Baugh J, Gantier M, Li L, Byrne A, Buckley A, Donnelly S. Dual regulation of macrophage migration inhibitory factor (MIF) expression in hypoxia by CREB and HIF-1. Biochem Biophys Res Commun. 2006;347:895-903 pubmed
    ..Given the importance of MIF in inflammatory and malignant diseases these data reveal a HIF-1-mediated pathway as a potential therapeutic target for suppression of MIF expression in hypoxic tissues. ..
  57. Yin L, Kharbanda S, Kufe D. Mucin 1 oncoprotein blocks hypoxia-inducible factor 1alpha activation in a survival response to hypoxia. J Biol Chem. 2007;282:257-66 pubmed
    ..Importantly, MUC1 also blocks hypoxia-induced apoptosis and necrosis by suppressing accumulation of ROS. These findings indicate that MUC1 attenuates HIF-1alpha activation in a survival response to hypoxic stress. ..
  58. Li S, Shin D, Chun Y, Lee M, Kim M, Park J. A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation from HIF-1{alpha}. Mol Cancer Ther. 2008;7:3729-38 pubmed publisher
    ..Given these results, we suggest that the functional inactivation of HIF-alpha contributes to the YC-1-induced deregulation of hypoxia-induced genes. ..
  59. Zhu K, Chan W, Heymach J, Wilkinson M, McConkey D. Control of HIF-1alpha expression by eIF2 alpha phosphorylation-mediated translational repression. Cancer Res. 2009;69:1836-43 pubmed publisher
    ..Our data established that PIs down-regulated HIF-1alpha expression in cells that display activation of the unfolded protein response by stimulating phosphorylation of eIF2alpha and inhibiting HIF-1alpha translation. ..
  60. Burrows N, Resch J, Cowen R, von Wasielewski R, Hoang Vu C, West C, et al. Expression of hypoxia-inducible factor 1 alpha in thyroid carcinomas. Endocr Relat Cancer. 2010;17:61-72 pubmed publisher
    ..Given the strong association of HIF-1 alpha with an aggressive disease phenotype and therapeutic resistance, this pathway may be an attractive target for improved therapy in thyroid carcinomas. ..
  61. Menrad H, Werno C, Schmid T, Copanaki E, Deller T, Dehne N, et al. Roles of hypoxia-inducible factor-1alpha (HIF-1alpha) versus HIF-2alpha in the survival of hepatocellular tumor spheroids. Hepatology. 2010;51:2183-92 pubmed publisher
    ..Our data indicate that enhanced expression of one HIF-isoform causes a survival advantage in hepatocellular carcinoma development. ..
  62. Botlagunta M, Krishnamachary B, Vesuna F, Winnard P, Bol G, Patel A, et al. Expression of DDX3 is directly modulated by hypoxia inducible factor-1 alpha in breast epithelial cells. PLoS ONE. 2011;6:e17563 pubmed publisher
  63. Rezvani H, Ali N, Nissen L, Harfouche G, de Verneuil H, Taieb A, et al. HIF-1? in epidermis: oxygen sensing, cutaneous angiogenesis, cancer, and non-cancer disorders. J Invest Dermatol. 2011;131:1793-805 pubmed publisher
    ..Here, we review the role of HIF-1? in cutaneous angiogenesis, skin tumorigenesis, and several skin disorders. ..
  64. Li P, Cao Q, Shao P, Cai H, Zhou H, Chen J, et al. Genetic polymorphisms in HIF1A are associated with prostate cancer risk in a Chinese population. Asian J Androl. 2012;14:864-9 pubmed publisher
    ..10; 95%CI=1.23-3.57 among subjects carrying three or more risk alleles). These results suggest that HIF1A polymorphisms may impact PCa susceptibility and progression in the Chinese Han population. ..
  65. Zhang Q, Bai X, Chen W, Ma T, Hu Q, Liang C, et al. Wnt/?-catenin signaling enhances hypoxia-induced epithelial-mesenchymal transition in hepatocellular carcinoma via crosstalk with hif-1? signaling. Carcinogenesis. 2013;34:962-73 pubmed publisher
    ..Our results suggest that Wnt/?-catenin signaling enhances hypoxia-induced EMT in HCC by increasing the EMT-associated activity of hif-1? and preventing tumor cell death. ..
  66. Bruick R, McKnight S. A conserved family of prolyl-4-hydroxylases that modify HIF. Science. 2001;294:1337-40 pubmed
    ..These findings indicate that HPH is an essential component of the pathway through which cells sense oxygen. ..
  67. Dames S, Martinez Yamout M, De Guzman R, Dyson H, Wright P. Structural basis for Hif-1 alpha /CBP recognition in the cellular hypoxic response. Proc Natl Acad Sci U S A. 2002;99:5271-6 pubmed
    ..The structure of this complex provides new insights into the mechanism through which Hif-1 alpha recruits CBP/p300 in response to hypoxia. ..
  68. Warnecke C, Zaborowska Z, Kurreck J, Erdmann V, Frei U, Wiesener M, et al. Differentiating the functional role of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha (EPAS-1) by the use of RNA interference: erythropoietin is a HIF-2alpha target gene in Hep3B and Kelly cells. FASEB J. 2004;18:1462-4 pubmed
    ..In conclusion, we found a remarkably restricted target gene specificity of the HIFalpha subunits, which can be overcome in cells with perturbations in the pVHL/HIF system and under forced expression. ..
  69. Konac E, Onen H, Metindir J, Alp E, Biri A, Ekmekci A. An investigation of relationships between hypoxia-inducible factor-1 alpha gene polymorphisms and ovarian, cervical and endometrial cancers. Cancer Detect Prev. 2007;31:102-9 pubmed
    ..Our results suggest that the C1772T polymorphism of the HIF-1 alpha may be associated with cervical and endometrial cancers. ..
  70. Deshmane S, Mukerjee R, Fan S, Del Valle L, Michiels C, Sweet T, et al. Activation of the oxidative stress pathway by HIV-1 Vpr leads to induction of hypoxia-inducible factor 1alpha expression. J Biol Chem. 2009;284:11364-73 pubmed publisher
  71. Dai C, Gao Q, Qiu S, Ju M, Cai M, Xu Y, et al. Hypoxia-inducible factor-1 alpha, in association with inflammation, angiogenesis and MYC, is a critical prognostic factor in patients with HCC after surgery. BMC Cancer. 2009;9:418 pubmed publisher
    ..It may influence HCC biological behaviors and affect the tumor inflammation, angiogenesis and act in concert with the oncogene MYC. Attaching importance to HIF-1alpha in HCC may improve the prognostic and therapeutic technique. ..
  72. Zhao J, Luo Y, Jiang Y, He D, Wu C. Knockdown of ?-Catenin through shRNA cause a reversal of EMT and metastatic phenotypes induced by HIF-1?. Cancer Invest. 2011;29:377-82 pubmed publisher
    ..Wnt/?-catenin signaling pathway might be a necessary endogenous signal that directly controlled the EMT occurrence induced by HIF-1?. ..
  73. McCormick R, Blick C, Ragoussis J, Schoedel J, Mole D, Young A, et al. miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis. Br J Cancer. 2013;108:1133-42 pubmed publisher
    ..We provide further evidence of miR-210 activity in vivo, and show that high miR-210 expression is associated with better clinico-pathological prognostic factors. ..
  74. Beasley N, Leek R, Alam M, Turley H, Cox G, Gatter K, et al. Hypoxia-inducible factors HIF-1alpha and HIF-2alpha in head and neck cancer: relationship to tumor biology and treatment outcome in surgically resected patients. Cancer Res. 2002;62:2493-7 pubmed
    ..Expression of HIF-1alpha in surgically treated patients with HNSCC (n = 79) was associated with improved disease-free survival (P = 0.016) and overall survival (P = 0.027). ..
  75. van Hagen M, Overmeer R, Abolvardi S, Vertegaal A. RNF4 and VHL regulate the proteasomal degradation of SUMO-conjugated Hypoxia-Inducible Factor-2alpha. Nucleic Acids Res. 2010;38:1922-31 pubmed publisher
    ..The ubiquitin E3 ligases von Hippel-Lindau and RNF4 control the levels of sumoylated HIF-2alpha, indicating that sumoylated HIF-2alpha is degraded via SUMO-targeted ubiquitin ligases. ..
  76. Maroni P, Matteucci E, Luzzati A, Perrucchini G, Bendinelli P, Desiderio M. Nuclear co-localization and functional interaction of COX-2 and HIF-1? characterize bone metastasis of human breast carcinoma. Breast Cancer Res Treat. 2011;129:433-50 pubmed publisher
    ..Our observations might be useful to design therapies against bone metastasis, by affecting the phenotype changes of metastatic cells occurring at the secondary growth site through COX-2-HIF-1 interaction. ..
  77. Min Y, Ghose S, Boelte K, Li J, Yang L, Lin P. C/EBP-? regulates VEGF-C autocrine signaling in lymphangiogenesis and metastasis of lung cancer through HIF-1?. Oncogene. 2011;30:4901-9 pubmed publisher
    ..Blocking HIF-1? activity totally blocked CEBP-?-induced VEGF-C and VEGFR3 expression in LECs. Together, these findings uncover a new function of CEBP-? in lymphangiogenesis through regulation of VEGFR3 signaling in LECs. ..
  78. Shibaji T, Nagao M, Ikeda N, Kanehiro H, Hisanaga M, Ko S, et al. Prognostic significance of HIF-1 alpha overexpression in human pancreatic cancer. Anticancer Res. 2003;23:4721-7 pubmed
    ..Therefore, assessment of HIF-1 alpha expression might be useful for predicting the prognosis of pancreatic cancer patients. ..
  79. Stiehl D, Jelkmann W, Wenger R, Hellwig Burgel T. Normoxic induction of the hypoxia-inducible factor 1alpha by insulin and interleukin-1beta involves the phosphatidylinositol 3-kinase pathway. FEBS Lett. 2002;512:157-62 pubmed
    ..We propose that PI3K signaling is not only important in the hypoxic induction of HIF-1 but it is also crucially involved in the response to insulin and IL-1. ..
  80. Luo F, Liu X, Yan N, Li S, Cao G, Cheng Q, et al. Hypoxia-inducible transcription factor-1alpha promotes hypoxia-induced A549 apoptosis via a mechanism that involves the glycolysis pathway. BMC Cancer. 2006;6:26 pubmed
    ..During hypoxia in A549 cells, HIF-1alpha promotes activity of the glycolysis pathway and decreases the pH of the culture medium, resulting in increased cellular apoptosis. ..
  81. Zhao T, Lv J, Zhao J, Nzekebaloudou M. Hypoxia-inducible factor-1alpha gene polymorphisms and cancer risk: a meta-analysis. J Exp Clin Cancer Res. 2009;28:159 pubmed publisher
    ..The association between the 1790 G/A polymorphism and lower breast cancer risk could be due to chance. ..
  82. Gothié E, Richard D, Berra E, Pages G, Pouyssegur J. Identification of alternative spliced variants of human hypoxia-inducible factor-1alpha. J Biol Chem. 2000;275:6922-7 pubmed
    ..As expected, this small isoform can compete with the endogenous and transfected full-length HIF-1alpha. Altogether, these results suggest that the HIF-1alpha(736) isoform modulates gene expression upon hypoxia. ..