Progress on hypoxia-inducible factor-3: Its structure, gene regulation and biological function (Review)
- Authors:
- Sheng‑Li Yang
- Chao Wu
- Zhi‑Fan Xiong
- Xiefan Fang
-
Affiliations: Department of General Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China, Department of Medicine and Division of Digestion Disease, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, P.R. China, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA - Published online on: April 27, 2015 https://doi.org/10.3892/mmr.2015.3689
- Pages: 2411-2416
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|
Rankin EB, Giaccia AJ and Schipani E: A central role for hypoxic signaling in cartilage, bone and hematopoiesis. Curr Osteoporos Rep. 9:46–52. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Loenarz C, Coleman ML, Boleininger A, et al: The hypoxia-inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerens. EMBO Rep. 12:63–70. 2011. View Article : Google Scholar | |
|
Semenza GL: Hypoxia-inducible factors in physiology and medicine. Cell. 148:399–408. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Greer SN, Metcalf JL, Wang Y and Ohh M: The updated biology of hypoxia-inducible factor. EMBO J. 31:2448–2460. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Goda N and Kanai M: Hypoxia-inducible factors and their roles in energy metabolism. Int J Hematol. 95:457–463. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Ye J, Wu D, Wu P, Chen Z and Huang J: The cancer stem cell niche: Cross talk between cancer stem cells and their microenvironment. Tumour Biol. 35:3945–3951. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Yang SL, Liu LP, Jiang JX, Xiong ZF, He QJ and Wu C: The correlation of expression levels of HIF-1α and HIF-2α in hepatocellular carcinoma with capsular invasion, portal vein tumor thrombi and patients’ clinical outcome. Jpn J Clin Oncol. 44:159–167. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Cao S, Yang S, Wu C, Wang Y, Jiang J and Lu Z: Protein expression of hypoxia-inducible factor-1 alpha and hepatocellular carcinoma: A systematic review with meta-analysis. Clin Res Hepatol Gastroenterol. 38:598–603. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Tsai YP and Wu KJ: Hypoxia-regulated target genes implicated in tumor metastasis. J Biomed Sci. 19:1022012. View Article : Google Scholar : PubMed/NCBI | |
|
Semenza GL and Wang GL: 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. 12:5447–5454. 1992.PubMed/NCBI | |
|
Tian H, McKnight SL and Russell DW: Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev. 11:72–82. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Gu YZ, Moran SM, Hogenesch JB, Wartman L and Bradfield CA: Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha. Gene Expr. 7:205–213. 1998.PubMed/NCBI | |
|
Hara S, Hamada J, Kobayashi C, Kondo Y and Imura N: Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: Suppression of HIF-mediated gene expression by HIF-3alpha. Biochem Biophys Res Commun. 287:808–813. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Ku JH, Park YH, Myung JK, Moon KC, Kwak C and Kim HH: Expression of hypoxia inducible factor-1α and 2α in conventional renal cell carcinoma with or without sarcomatoid differentiation. Urol Oncol. 29:731–737. 2011. View Article : Google Scholar | |
|
Luan Y, Gao C, Miao Y, Li Y, Wang Z and Qiu X: Clinicopathological and prognostic significance of HIF-1α and HIF-2α expression in small cell lung cancer. Pathol Res Pract. 209:184–189. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kroeger N, Seligson DB, Signoretti S, et al: Poor prognosis and advanced clinicopathological features of clear cell renal cell carcinoma (ccRCC) are associated with cytoplasmic subcellular localisation of Hypoxia inducible factor-2α. Eur J Cancer. 50:1531–1540. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Gong L, Zhang W, Zhou J, et al: Prognostic value of HIFs expression in head and neck cancer: A systematic review. PLoS One. 8:e750942013. View Article : Google Scholar : PubMed/NCBI | |
|
Augstein A, Poitz DM, Braun-Dullaeus RC, Strasser RH and Schmeisser A: Cell-specific and hypoxia-dependent regulation of human HIF-3α: Inhibition of the expression of HIF target genes in vascular cells. Cell Mol Life Sci. 68:2627–2642. 2011. View Article : Google Scholar | |
|
Zhang P, Yao Q, Lu L, Li Y, Chen PJ and Duan C: Hypoxia-inducible factor 3 is an oxygen-dependent transcription activator and regulates a distinct transcriptional response to hypoxia. Cell Reports. 6:1110–1121. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Semenza GL: Hypoxia-inducible factor 1: Master regulator of O2 homeostasis. Curr Opin Genet Dev. 8:588–594. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Pasanen A, Heikkila M, Rautavuoma K, Hirsila M, Kivirikko KI and Myllyharju J: Hypoxia-inducible factor (HIF)-3alpha is subject to extensive alternative splicing in human tissues and cancer cells and is regulated by HIF-1 but not HIF-2. Int J Biochem Cell Biol. 42:1189–1200. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Maynard MA, Qi H, Chung J, 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. 278:11032–11040. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Huang LE, Arany Z, Livingston DM and Bunn HF: Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit. J Biol Chem. 271:32253–32259. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
Whitelaw ML, Gustafsson JA and Poellinger L: Identification of transactivation and repression functions of the dioxin receptor and its basic helix-loop-helix/PAS partner factor Arnt: inducible versus constitutive modes of regulation. Mol Cell Biol. 14:8343–8355. 1994.PubMed/NCBI | |
|
Reyes H, Reisz-Porszasz S and Hankinson O: Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor. Science. 256:1193–1195. 1992. View Article : Google Scholar : PubMed/NCBI | |
|
Makino Y, Kanopka A, Wilson WJ, Tanaka H and Poellinger L: Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3alpha locus. J Biol Chem. 277:32405–32408. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Makino Y, Cao R, Svensson K, et al: Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature. 414:550–554. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Yamashita T, Ohneda O, Nagano M, et al: Abnormal heart development and lung remodeling in mice lacking the hypoxia-inducible factor-related basic helix-loop-helix PAS protein NEPAS. Mol Cell Biol. 28:1285–1297. 2008. View Article : Google Scholar : | |
|
Majmundar AJ, Wong WJ and Simon MC: Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 40:294–309. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Li QF, Wang XR, Yang YW and Lin H: Hypoxia upregulates hypoxia inducible factor (HIF)-3alpha expression in lung epithelial cells: Characterization and comparison with HIF-1alpha. Cell Res. 16:548–558. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Tanaka T, Wiesener M, Bernhardt W, Eckardt KU and Warnecke C: The human HIF (hypoxia-inducible factor)-3alpha gene is a HIF-1 target gene and may modulate hypoxic gene induction. Biochem J. 424:143–151. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Heidbreder M, Frohlich F, Johren O, Dendorfer A, Qadri F and Dominiak P: Hypoxia rapidly activates HIF-3alpha mRNA expression. FASEB J. 17:1541–1543. 2003.PubMed/NCBI | |
|
Rajatapiti P, de Rooij JD, Beurskens LW, et al: Effect of oxygen on the expression of hypoxia-inducible factors in human fetal lung explants. Neonatology. 97:346–354. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Li QF and Dai AG: Differential expression of three hypoxia-inducible factor-alpha subunits in pulmonary arteries of rat with hypoxia-induced hypertension. Acta Biochim Biophys Sin (Shanghai). 37:665–672. 2005. View Article : Google Scholar | |
|
Zhang P, Lu L, Yao Q, et al: Molecular, functional and gene expression analysis of zebrafish hypoxia-inducible factor-3alpha. Am J Physiol Regul Integr Comp Physiol. 303:R1165–R1174. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Makino Y, Uenishi R, Okamoto K, et al: Transcriptional up-regulation of inhibitory PAS domain protein gene expression by hypoxia-inducible factor 1 (HIF-1): a negative feedback regulatory circuit in HIF-1-mediated signaling in hypoxic cells. J Biol Chem. 282:14073–14082. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Hatanaka M, Shimba S, Sakaue M, et al: Hypoxia-inducible factor-3alpha functions as an accelerator of 3T3-L1 adipose differentiation. Biol Pharm Bull. 32:1166–1172. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Heidbreder M, Qadri F, Johren O, et al: Non-hypoxic induction of HIF-3alpha by 2-deoxy-D-glucose and insulin. Biochem Biophys Res Commun. 352:437–443. 2007. View Article : Google Scholar | |
|
Choueiri TK, Fay AP, Gagnon R, et al: The role of aberrant VHL/HIF pathway elements in predicting clinical outcome to pazopanib therapy in patients with metastatic clear-cell renal cell carcinoma. Clin Cancer Res. 19:5218–5226. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kennedy BK: A new connection between VHL and cancer threads through progerin. Cell Cycle. 12:2721–2722. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Bausch B, Jilg C, Glasker S, et al: Renal cancer in von Hippel-Lindau disease and related syndromes. Nat Rev Nephrol. 9:529–538. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Pientka FK, Hu J, Schindler SG, et al: Oxygen sensing by the prolyl-4-hydroxylase PHD2 within the nuclear compartment and the influence of compartmentalisation on HIF-1 signalling. J Cell Sci. 125:5168–5176. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Niecknig H, Tug S, Reyes BD, Kirsch M, Fandrey J and Berchner-Pfannschmidt U: Role of reactive oxygen species in the regulation of HIF-1 by prolyl hydroxylase 2 under mild hypoxia. Free Radic Res. 46:705–717. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Groulx I and Lee S: Oxygen-dependent ubiquitination and degradation of hypoxia-inducible factor requires nuclear-cytoplasmic trafficking of the von Hippel-Lindau tumor suppressor protein. Mol Cell Biol. 22:5319–5336. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Ivan M, Kondo K, Yang H, et al: HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science. 292:464–468. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Chen YR, Dai AG, Hu RC and Jiang YL: Differential and reciprocal regulation between hypoxia-inducible factor-alpha subunits and their prolyl hydroxylases in pulmonary arteries of rat with hypoxia-induced hypertension. Acta Biochim Biophys Sin (Shanghai). 38:423–434. 2006. View Article : Google Scholar | |
|
Harvey AJ, Kind KL and Thompson JG: Regulation of gene expression in bovine blastocysts in response to oxygen and the iron chelator desferrioxamine. Biol Reprod. 77:93–101. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Woo KJ, Lee TJ, Park JW and Kwon TK: Desferrioxamine, an iron chelator, enhances HIF-1alpha accumulation via cyclooxygenase-2 signaling pathway. Biochem Biophys Res Commun. 343:8–14. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Triantafyllou A, Liakos P, Tsakalof A, Georgatsou E, Simos G and Bonanou S: Cobalt induces hypoxia-inducible factor-1alpha (HIF-1alpha) in HeLa cells by an iron-independent, but ROS-, PI-3K- and MAPK-dependent mechanism. Free Radic Res. 40:847–856. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Yuan Y, Hilliard G, Ferguson T and Millhorn DE: Cobalt inhibits the interaction between hypoxia-inducible factor-alpha and von Hippel-Lindau protein by direct binding to hypoxia-inducible factor-alpha. J Biol Chem. 278:15911–15916. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Wu D, Zhang R, Zhao R, Chen G, Cai Y and Jin J: A novel function of novobiocin: Disrupting the interaction of HIF 1alpha and p300/CBP through direct binding to the HIF1alpha C-terminal activation domain. PLoS One. 8:e620142013. View Article : Google Scholar | |
|
Mendonca DB, Mendonca G, Aragao FJ and Cooper LF: NF-kappaB suppresses HIF-1alpha response by competing for P300 binding. Biochem Biophys Res Commun. 404:997–1003. 2011. View Article : Google Scholar | |
|
Maynard MA, Evans AJ, Hosomi T, Hara S, Jewett MA and Ohh M: Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma. FASEB J. 19:1396–1406. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Maynard MA, Evans AJ, Shi W, Kim WY, Liu FF and Ohh M: Dominant-negative HIF-3 alpha 4 suppresses VHL-null renal cell carcinoma progression. Cell Cycle. 6:2810–2816. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Ando H, Natsume A, Iwami K, et al: A hypoxia-inducible factor (HIF)-3alpha splicing variant, HIF-3alpha4 impairs angiogenesis in hypervascular malignant meningiomas with epigenetically silenced HIF-3alpha4. Biochem Biophys Res Commun. 433:139–144. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Shah YM and Xie L: Hypoxia-inducible factors link iron homeostasis and erythropoiesis. Gastroenterology. 146:630–642. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Haase VH: Regulation of erythropoiesis by hypoxia-inducible factors. Blood Rev. 27:41–53. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Li H, Ge C, Zhao F, et al: Hypoxia-inducible factor 1 alpha-activated angiopoietin-like protein 4 contributes to tumor metastasis via vascular cell adhesion molecule-1/integrin beta1 signaling in human hepatocellular carcinoma. Hepatology. 54:910–919. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Imamura T, Kikuchi H, Herraiz MT, et al: HIF-1alpha and HIF-2alpha have divergent roles in colon cancer. Int J Cancer. 124:763–771. 2009. View Article : Google Scholar : | |
|
Marin-Hernandez A, Gallardo-Perez JC, Ralph SJ, Rodriguez-Enriquez S and Moreno-Sanchez R: HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem. 9:1084–1101. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Airley RE and Mobasheri A: Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: Novel pathways and targets for anticancer therapeutics. Chemotherapy. 53:233–256. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Heikkila M, Pasanen A, Kivirikko KI and Myllyharju J: Roles of the human hypoxia-inducible factor (HIF)-3alpha variants in the hypoxia response. Cell Mol Life Sci. 68:3885–3901. 2011. View Article : Google Scholar | |
|
Deshmukh AB, Patel JK, Prajapati AR and Shah S: Perspective in chronic kidney disease: targeting hypoxia-inducible factor (HIF) as potential therapeutic approach. Ren Fail. 34:521–532. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Kones R: Oxygen therapy for acute myocardial infarction-then and now. A century of uncertainty. Am J Med. 124:1000–1005. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Shi H: Hypoxia inducible factor 1 as a therapeutic target in ischemic stroke. Curr Med Chem. 16:4593–4600. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Lee SH, Wolf PL, Escudero R, Deutsch R, Jamieson SW and Thistlethwaite PA: Early expression of angiogenesis factors in acute myocardial ischemia and infarction. N Engl J Med. 342:626–633. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Zolk O, Solbach TF, Eschenhagen T, Weidemann A and Fromm MF: Activation of negative regulators of the hypoxia-inducible factor (HIF) pathway in human end-stage heart failure. Biochem Biophys Res Commun. 376:315–320. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Yoshida T, Kuwahara M, Maita K and Harada T: Immunohistochemical study on hypoxia in spontaneous poly-cystic liver and kidney disease in rats. Exp Toxicol Pathol. 53:123–128. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Fang HY, Lin CY, Chow KC, Huang HC and Ko WJ: Microarray detection of gene overexpression in primary spontaneous pneumothorax. Exp Lung Res. 36:323–330. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Drevytska T, Gavenauskas B, Drozdovska S, Nosar V, Dosenko V and Mankovska I: HIF-3alpha mRNA expression changes in different tissues and their role in adaptation to intermittent hypoxia and physical exercise. Pathophysiology. 19:205–214. 2012. View Article : Google Scholar : PubMed/NCBI |
