HIF-1 alpha


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. van De Sluis B, Groot A, Vermeulen J, van der Wall E, van Diest P, Wijmenga C, et al. COMMD1 Promotes pVHL and O2-Independent Proteolysis of HIF-1alpha via HSP90/70. PLoS ONE. 2009;4:e7332 pubmed publisher
    ..These data reveal a novel role for COMMD1 in conjunction with HSP90beta/HSP70 in the ubiquitin and O(2)-independent regulation of HIF-1alpha. ..
  2. 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. ..
  3. 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. ..
  4. 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. ..
  5. 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. ..
  6. 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. ..
  7. 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. ..
  8. 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...
  9. 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. ..

More Information

Publications470 found, 100 shown here

  1. 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. ..
  2. 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. ..
  3. 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. ..
  4. 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. ..
  5. 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. ..
  6. 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. ..
  7. 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. ..
  8. Ogunshola O, Antoniou X. Contribution of hypoxia to Alzheimer's disease: is HIF-1alpha a mediator of neurodegeneration?. Cell Mol Life Sci. 2009;66:3555-63 pubmed publisher
  9. 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. ..
  10. 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. ..
  11. Warfel N, Dolloff N, Dicker D, Malysz J, El Deiry W. CDK1 stabilizes HIF-1? via direct phosphorylation of Ser668 to promote tumor growth. Cell Cycle. 2013;12:3689-701 pubmed publisher
  12. 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. ..
  13. 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. ..
  14. 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. ..
  15. 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. ..
  16. 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. ..
  17. 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. ..
  18. 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. ..
  19. 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. ..
  20. Nakamura J, Kitajima Y, Kai K, Hashiguchi K, Hiraki M, Noshiro H, et al. HIF-1alpha is an unfavorable determinant of relapse in gastric cancer patients who underwent curative surgery followed by adjuvant 5-FU chemotherapy. Int J Cancer. 2010;127:1158-71 pubmed publisher
  21. 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...
  22. 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...
  23. Culver C, Melvin A, Mudie S, Rocha S. HIF-1α depletion results in SP1-mediated cell cycle disruption and alters the cellular response to chemotherapeutic drugs. Cell Cycle. 2011;10:1249-60 pubmed
    ..These data have important implications in not only for the further understanding of HIF-1α, a major transcription factor, but also for the use of HIF-targeted and combination therapies in cancer treatment. ..
  24. Yang C, Huntoon K, Ksendzovsky A, Zhuang Z, Lonser R. Proteostasis modulators prolong missense VHL protein activity and halt tumor progression. Cell Rep. 2013;3:52-9 pubmed publisher
    ..These findings provide direct biological insight into VHL-associated tumors and elucidate a treatment paradigm for VHL. ..
  25. Li J, Xu Y, Long X, Wang W, Jiao H, Mei Z, et al. Cbx4 governs HIF-1? to potentiate angiogenesis of hepatocellular carcinoma by its SUMO E3 ligase activity. Cancer Cell. 2014;25:118-31 pubmed publisher
    ..Collectively, our findings demonstrate that Cbx4 plays a critical role in tumor angiogenesis by governing HIF-1? protein. ..
  26. Rajakumar A, Conrad K. Expression, ontogeny, and regulation of hypoxia-inducible transcription factors in the human placenta. Biol Reprod. 2000;63:559-69 pubmed
  27. Hewitson K, McNeill L, Riordan M, Tian Y, Bullock A, Welford R, et al. Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J Biol Chem. 2002;277:26351-5 pubmed
  28. Qian D, Kachhap S, Collis S, Verheul H, Carducci M, Atadja P, et al. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Res. 2006;66:8814-21 pubmed
    ..Taken together, these results suggest that class II HDACs are associated with HIF-1 alpha stability and provide a rationale for targeting HIF-1 alpha with HDAC inhibitors against class II isozymes. ..
  29. Xu Z, Chen X, Peng C, Liu E, Li Y, Li C, et al. Hypoxia-inducible factor-1alpha suppressed hepatocellular carcinoma cell apoptosis through influencing on Omi/HtrA2 expression and its releasing from the mitochondrion. Oncol Res. 2012;20:213-20 pubmed
    ..The present finding further enriched and supported the role of HIF-1alpha expression on cell apoptosis of hepatoma cells. ..
  30. Huang L, Gu J, Schau M, Bunn H. Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A. 1998;95:7987-92 pubmed
    ..Hence, the ODD domain plays a pivotal role for regulating HIF-1 activity and thereby may provide a means of controlling gene expression by changes in oxygen tension. ..
  31. Lim J, Lee E, You H, Lee J, Park J, Chun Y. Ras-dependent induction of HIF-1alpha785 via the Raf/MEK/ERK pathway: a novel mechanism of Ras-mediated tumor promotion. Oncogene. 2004;23:9427-31 pubmed
    ..These results imply that HIF-1alpha(785) may play an important role in tumor promotion mediated by the Ras oncogene, phorbol ester or tumor growth factors. ..
  32. Thomas G, Tran C, Mellinghoff I, Welsbie D, Chan E, Fueger B, et al. Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat Med. 2006;12:122-7 pubmed
    ..Our findings provide preclinical rationale for prospective, biomarker-driven clinical studies of mTOR inhibitors in kidney cancer and suggest that FDG-PET scans may have use as a pharmacodynamic marker in this setting. ..
  33. Sasabe E, Zhou X, Li D, Oku N, Yamamoto T, Osaki T. The involvement of hypoxia-inducible factor-1alpha in the susceptibility to gamma-rays and chemotherapeutic drugs of oral squamous cell carcinoma cells. Int J Cancer. 2007;120:268-77 pubmed
    ..These results suggest that enhanced HIF-1alpha expression is related to the resistance of tumor cells to chemo- and radio-therapy and that HIF-1alpha is an effective therapeutic target for cancer treatment. ..
  34. Gordan J, Bertout J, Hu C, Diehl J, Simon M. HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell. 2007;11:335-47 pubmed
    ..Enhanced c-Myc activity likely contributes to HIF-2alpha-mediated neoplastic progression following loss of the VHL tumor suppressor and influences the behavior of hypoxic tumor cells. ..
  35. Cascio S, Bartella V, Auriemma A, Johannes G, Russo A, Giordano A, et al. Mechanism of leptin expression in breast cancer cells: role of hypoxia-inducible factor-1alpha. Oncogene. 2008;27:540-7 pubmed
    ..The importance of HIF-1alpha in insulin- and CoCl2-activated leptin mRNA and protein expression was confirmed using RNA interference. ..
  36. Nardinocchi L, Puca R, Guidolin D, Belloni A, Bossi G, Michiels C, et al. Transcriptional regulation of hypoxia-inducible factor 1alpha by HIPK2 suggests a novel mechanism to restrain tumor growth. Biochim Biophys Acta. 2009;1793:368-77 pubmed publisher
    ..These findings provide the first evidence of HIPK2-mediated transcriptional regulation of HIF-1alpha that might play a critical role in VEGF expression. ..
  37. Rohwer N, Dame C, Haugstetter A, Wiedenmann B, Detjen K, Schmitt C, et al. Hypoxia-inducible factor 1alpha determines gastric cancer chemosensitivity via modulation of p53 and NF-kappaB. PLoS ONE. 2010;5:e12038 pubmed publisher
    ..We conclude that p53 mutations in human tumors hold the potential to confound the efficacy of HIF-1-inhibitors in cancer therapy. ..
  38. Chen R, Dioum E, Hogg R, Gerard R, Garcia J. Hypoxia increases sirtuin 1 expression in a hypoxia-inducible factor-dependent manner. J Biol Chem. 2011;286:13869-78 pubmed publisher
    ..We also find that Sirt1 augments HIF-2 mediated, but not HIF-1 mediated, transcriptional activation of the isolated Sirt1 promoter. These data in summary reveal a bidirectional link of HIF and Sirt1 signaling during hypoxia. ..
  39. Hubbi M, Kshitiz -, Gilkes D, Rey S, Wong C, Luo W, et al. A nontranscriptional role for HIF-1? as a direct inhibitor of DNA replication. Sci Signal. 2013;6:ra10 pubmed publisher
    ..These findings establish a transcription-independent mechanism by which the stabilization of HIF-1? leads to cell cycle arrest in response to hypoxia. ..
  40. 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. ..
  41. Kallio P, Okamoto K, O BRIEN S, Carrero P, Makino Y, Tanaka H, et al. Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1alpha. EMBO J. 1998;17:6573-86 pubmed
    ..Thus, hypoxia-inducible nuclear import and transactivation by recruitment of CBP can be functionally separated from one another and play critical roles in signal transduction by HIF-1alpha. ..
  42. Stoeltzing O, McCarty M, Wey J, Fan F, Liu W, Belcheva A, et al. Role of hypoxia-inducible factor 1alpha in gastric cancer cell growth, angiogenesis, and vessel maturation. J Natl Cancer Inst. 2004;96:946-56 pubmed
    ..Inhibition of HIF-1alpha activity impairs gastric tumor growth, angiogenesis, and vessel maturation. ..
  43. 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. ..
  44. BelAiba R, Bonello S, Zähringer C, Schmidt S, Hess J, Kietzmann T, et al. Hypoxia up-regulates hypoxia-inducible factor-1alpha transcription by involving phosphatidylinositol 3-kinase and nuclear factor kappaB in pulmonary artery smooth muscle cells. Mol Biol Cell. 2007;18:4691-7 pubmed
    ..Together, these findings provide a novel mechanism in which hypoxia induces HIF-1alpha mRNA expression via the PI3K/AKT pathway and activation of NFkappaB. ..
  45. 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. ..
  46. 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. ..
  47. 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. ..
  48. Dales J, Beaufils N, Silvy M, Picard C, Pauly V, Pradel V, et al. Hypoxia inducible factor 1alpha gene (HIF-1alpha) splice variants: potential prognostic biomarkers in breast cancer. BMC Med. 2010;8:44 pubmed publisher
    ..See commentary: http://www.biomedcentral.com/1741-7015/8/45. ..
  49. 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. ..
  50. 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. ..
  51. Bahadori B, Uitz E, Mayer A, Harauer J, Dam K, Truschnig Wilders M, et al. Polymorphisms of the hypoxia-inducible factor 1 gene and peripheral artery disease. Vasc Med. 2010;15:371-4 pubmed publisher
    Hypoxia-inducible factor 1 (HIF1) is a key regulator of angiogenesis and is involved in inflammation, which are two important features of the pathogenesis of peripheral artery disease (PAD)...
  52. 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. ..
  53. 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. ..
  54. 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). ..
  55. Sumbayev V, Budde A, Zhou J, Brüne B. HIF-1 alpha protein as a target for S-nitrosation. FEBS Lett. 2003;535:106-12 pubmed
    ..In conclusion, HIF-1 alpha is a target for S-nitrosation by exogenously and endogenously produced NO. ..
  56. Manalo D, Rowan A, Lavoie T, Natarajan L, Kelly B, Ye S, et al. Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. Blood. 2005;105:659-69 pubmed
  57. 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
  58. 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. ..
  59. 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. ..
  60. 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. ..
  61. 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. ..
  62. Iyer N, Leung S, Semenza G. The human hypoxia-inducible factor 1alpha gene: HIF1A structure and evolutionary conservation. Genomics. 1998;52:159-65 pubmed
    ..The proximal 300 bp of 5' flanking sequences was 83% identical, including the SP1 sites and transcription initiation sites. These results suggest evolutionary selection for maintenance of HIF1A structure, function, and regulation. ..
  63. 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. ..
  64. 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
  65. 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. ..
  66. 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. ..
  67. 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. ..
  68. Lim W, Cho J, Kwon H, Park Y, Rhyu M, Lee Y. Hypoxia-inducible factor 1 alpha activates and is inhibited by unoccupied estrogen receptor beta. FEBS Lett. 2009;583:1314-8 pubmed publisher
    ..We then examined the effect of ER beta on HIF1-alpha transactivation...
  69. 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
  70. 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. ..
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    ..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...
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    ..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. ..
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    ..Future screening of the polymorphic HIF-1alpha allele may therefore be of importance in the selection of treatment strategies of CRC. ..
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    ..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. ..
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    ..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. ..
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