ARNT / HIF-1-Beta

Transcriptional responses to many environmental and developmental stimuli are mediated by the basic helix-loop-helix (bHLH)-PAS family of proteins, which form homodimers that bind regulatory DNA sequences. ARNT/HIF-1 beta regulates the expression of different sets of genes in response to distinct environmental challenges. ARNT forms a complex with arylhydrocarbon receptor (AHR) to activate expression of genes encoding P450. Once AHR binds it ligand, it associates with ARNT for transport into the nucleus. ARNT also dimerizes with HIF-1alpha, -2 alpha or -3 alpha in response to low oxygen concentration to induce the expression of hypoxia-regulated genes encoding vascular endothelial growth and other genes. The expression of ARNT/HIF-1beta remains fairly constant and the protein is found in the nucleus and the cytoplasm.

Publications (64)

Expression of hypoxia-inducible factor 1alpha in brain tumors: association with angiogenesis, invasion, and progression. Zagzag D, Zhong H, Scalzitti JM, Laughner E, Simons JW, Semenza GL. Cancer. 2000 88:2606-18. [PubMed:10861440]

Normoxic stabilization of hypoxia-inducible factor-1 expression and activity: redox-dependent effect of nitrogen oxides. Palmer LA, Gaston B, Johns RA. Molecular pharmacology. 2000 58:1197-203. [PubMed:11093754]

Hypoxia-inducible factor 1alpha and 1beta proteins share common signaling pathways in human prostate cancer cells. Zhong H, Hanrahan C, van der Poel H, Simons JW. Biochemical and biophysical research communications. 2001 284:352-6. [PubMed:11394885]

Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cells. Mabjeesh NJ, Post DE, Willard MT, Kaur B, Van Meir EG, Simons JW, Zhong H. Cancer research. 2002 62:2478-82. [PubMed:11980636]

Brain genomic response following hypoxia and re-oxygenation in the neonatal rat. Identification of genes that might contribute to hypoxia-induced ischemic tolerance. Bernaudin M, Tang Y, Reilly M, Petit E, Sharp FR. The Journal of biological chemistry. 2002 277:39728-38. [PubMed:12145288]

Identification of small molecule inhibitors of hypoxia-inducible factor 1 transcriptional activation pathway. Rapisarda A, Uranchimeg B, Scudiero DA, Selby M, Sausville EA, Shoemaker RH, Melillo G. Cancer research. 2002 62:4316-24. [PubMed:12154035]

Protein expression profiles indicative for drug resistance of non-small cell lung cancer. Volm M, Koomgi R, Mattern J, Efferth T. British journal of cancer. 2002 87:251-7. [PubMed:12177790] [PMC:PMC2364224]

Cooperative interaction of hypoxia-inducible factor-2alpha (HIF-2alpha ) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). Elvert G, Kappel A, Heidenreich R, Englmeier U, Lanz S, Acker T, Rauter M, Plate K, Sieweke M, Breier G, Flamme I. The Journal of biological chemistry. 2003 278:7520-30. [PubMed:12464608]

Dibenzoylmethane, a natural dietary compound, induces HIF-1 alpha and increases expression of VEGF. Mabjeesh NJ, Willard MT, Harris WB, Sun HY, Wang R, Zhong H, Umbreit JN, Simons JW. Biochemical and biophysical research communications. 2003 303:279-86. [PubMed:12646199]

2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Mabjeesh NJ, Escuin D, LaVallee TM, Pribluda VS, Swartz GM, Johnson MS, Willard MT, Zhong H, Simons JW, Giannakakou P. Cancer cell. 2003 3:363-75. [PubMed:12726862]

Vascular endothelial growth factor gene expression in colon cancer cells exposed to prostaglandin E2 is mediated by hypoxia-inducible factor 1. Fukuda R, Kelly B, Semenza GL. Cancer research. 2003 63:2330-4. [PubMed:12727858]

Follicle-stimulating hormone activation of hypoxia-inducible factor-1 by the phosphatidylinositol 3-kinase/AKT/Ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) pathway is necessary for induction of select protein markers of follic. Alam H, Maizels ET, Park Y, Ghaey S, Feiger ZJ, Chandel NS, Hunzicker-Dunn M. The Journal of biological chemistry. 2004 279:19431-40. [PubMed:14982927] [PMC:PMC1564189]

Topoisomerase I-mediated inhibition of hypoxia-inducible factor 1: mechanism and therapeutic implications. Rapisarda A, Uranchimeg B, Sordet O, Pommier Y, Shoemaker RH, Melillo G. Cancer research. 2004 64:1475-82. [PubMed:14983893]

Greater vascularity, lowered HIF-1/DNA binding, and elevated GSH as markers of adaptation to in vivo chronic hypoxia. Tissot van Patot MC, Bendrick-Peart J, Beckey VE, Serkova N, Zwerdlinger L. American journal of physiology. Lung cellular and molecular physiology. 2004 287:L525-32. [PubMed:15132953]

Autocrine effects of IGF-I-induced VEGF and IGFBP-3 secretion in retinal pigment epithelial cell line ARPE-19. Slomiany MG, Rosenzweig SA. American journal of physiology. Cell physiology. 2004 287:C746-53. [PubMed:15140752]

Akt and hypoxia-inducible factor-1 independently enhance tumor growth and angiogenesis. Arsham AM, Plas DR, Thompson CB, Simon MC. Cancer research. 2004 64:3500-7. [PubMed:15150104]

IGF-1-induced VEGF and IGFBP-3 secretion correlates with increased HIF-1 alpha expression and activity in retinal pigment epithelial cell line D407. Slomiany MG, Rosenzweig SA. Investigative ophthalmology & visual science. 2004 45:2838-47. [PubMed:15277511]

Induction of hypoxia-inducible factor 1 activity by muscarinic acetylcholine receptor signaling. Hirota K, Fukuda R, Takabuchi S, Kizaka-Kondoh S, Adachi T, Fukuda K, Semenza GL. The Journal of biological chemistry. 2004 279:41521-8. [PubMed:15280370]

Hypoxia and hypoxia-inducible factor-1alpha promote growth factor-induced proliferation of human vascular smooth muscle cells. Schultz K, Fanburg BL, Beasley D. American journal of physiology. Heart and circulatory physiology. 2006 290:H2528-34. [PubMed:16399861]

MSF-A interacts with hypoxia-inducible factor-1alpha and augments hypoxia-inducible factor transcriptional activation to affect tumorigenicity and angiogenesis. Amir S, Wang R, Matzkin H, Simons JW, Mabjeesh NJ. Cancer research. 2006 66:856-66. [PubMed:16424018]

Activation of hypoxia-inducible factor 1 during macrophage differentiation. Oda T, Hirota K, Nishi K, Takabuchi S, Oda S, Yamada H, Arai T, Fukuda K, Kita T, Adachi T, Semenza GL, Nohara R. American journal of physiology. Cell physiology. 2006 291:C104-13. [PubMed:16481368]

Calcium signaling stimulates translation of HIF-alpha during hypoxia. Hui AS, Bauer AL, Striet JB, Schnell PO, Czyzyk-Krzeska MF. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2006 20:466-75. [PubMed:16507764]

Expression of vascular endothelial growth factor receptor 1 in bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1. Okuyama H, Krishnamachary B, Zhou YF, Nagasawa H, Bosch-Marce M, Semenza GL. The Journal of biological chemistry. 2006 281:15554-63. [PubMed:16574650]

Differential regulation of the transcriptional activities of hypoxia-inducible factor 1 alpha (HIF-1alpha) and HIF-2alpha in stem cells. Hu CJ, Iyer S, Sataur A, Covello KL, Chodosh LA, Simon MC. Molecular and cellular biology. 2006 26:3514-26. [PubMed:16611993] [PMC:PMC1447431]

Brain-derived neurotrophic factor activation of TrkB induces vascular endothelial growth factor expression via hypoxia-inducible factor-1alpha in neuroblastoma cells. Nakamura K, Martin KC, Jackson JK, Beppu K, Woo CW, Thiele CJ. Cancer research. 2006 66:4249-55. [PubMed:16618748]

Improved lung growth and function through hypoxia-inducible factor in primate chronic lung disease of prematurity. Asikainen TM, Chang LY, Coalson JJ, Schneider BK, Waleh NS, Ikegami M, Shannon JM, Winter VT, Grubb P, Clyman RI, Yoder BA, Crapo JD, White CW. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2006 20:1698-700. (WB; Human) [PubMed:16807366]

HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Zhang H, Gao P, Fukuda R, Kumar G, Krishnamachary B, Zeller KI, Dang CV, Semenza GL. Cancer cell. 2007 11:407-20. [PubMed:17482131]

Spermidine/spermine-N1-acetyltransferase 2 is an essential component of the ubiquitin ligase complex that regulates hypoxia-inducible factor 1alpha. Baek JH, Liu YV, McDonald KR, Wesley JB, Hubbi ME, Byun H, Semenza GL. The Journal of biological chemistry. 2007 282:23572-80. [PubMed:17558023]

Involvement of chloride channels in TGF-beta1-induced apoptosis of human bronchial epithelial cells. Cheng G, Shao Z, Chaudhari B, Agrawal DK. American journal of physiology. Lung cellular and molecular physiology. 2007 293:L1339-47. [PubMed:17873007]

Spermidine/spermine N(1)-acetyltransferase-1 binds to hypoxia-inducible factor-1alpha (HIF-1alpha) and RACK1 and promotes ubiquitination and degradation of HIF-1alpha. Baek JH, Liu YV, McDonald KR, Wesley JB, Zhang H, Semenza GL. The Journal of biological chemistry. 2007 282:33358-66. [PubMed:17875644]

Acute hypobaric hypoxia (5486 m) induces greater pulmonary HIF-1 activation in hilltop compared to madison rats. Engebretsen BJ, Irwin D, Valdez ME, O'Donovan MK, Tucker A, van Patot MT. High altitude medicine & biology. 2007 8:312-21. [PubMed:18081507]

(2R)-[(4-Biphenylylsulfonyl)amino]-N-hydroxy-3-phenylpropionamide (BiPS), a matrix metalloprotease inhibitor, is a novel and potent activator of hypoxia-inducible factors. Lauzier MC, Robitaille GA, Chan DA, Giaccia AJ, Richard DE. Molecular pharmacology. 2008 74:282-8. (WB; Human) [PubMed:18424552] [PMC:PMC3050611]

Antioxidants, HIF prolyl hydroxylase inhibitors or short interfering RNAs to BNIP3 or PUMA, can prevent prodeath effects of the transcriptional activator, HIF-1alpha, in a mouse hippocampal neuronal line. Aminova LR, Siddiq A, Ratan RR. Antioxidants & redox signaling. 2008 10:1989-98. [PubMed:18774900] [PMC:PMC2612757]

Role of the phosphatidylinositol-3-kinase and extracellular regulated kinase pathways in the induction of hypoxia-inducible factor (HIF)-1 activity and the HIF-1 target vascular endothelial growth factor in ovarian granulosa cells in response to follicle-. Alam H, Weck J, Maizels E, Park Y, Lee EJ, Ashcroft M, Hunzicker-Dunn M. Endocrinology. 2009 150:915-28. [PubMed:18845636] [PMC:PMC2646536]

Hypoxia-inducible factor-1alpha is constitutively expressed in murine Leydig cells and regulates 3beta-hydroxysteroid dehydrogenase type 1 promoter activity. Lysiak JJ, Kirby JL, Tremblay JJ, Woodson RI, Reardon MA, Palmer LA, Turner TT. Journal of andrology. 30:146-56. [PubMed:18930903]

Lung development in the Holtzman rat is adversely affected by gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Kransler KM, McGarrigle BP, Swartz DD, Olson JR. Toxicological sciences : an official journal of the Society of Toxicology. 2009 107:498-511. [PubMed:18990726]

SEPT9_v1 up-regulates hypoxia-inducible factor 1 by preventing its RACK1-mediated degradation. Amir S, Wang R, Simons JW, Mabjeesh NJ. The Journal of biological chemistry. 2009 284:11142-51. [PubMed:19251694] [PMC:PMC2670119]

Dynamic changes in presynaptic and axonal transport proteins combined with striatal neuroinflammation precede dopaminergic neuronal loss in a rat model of AAV alpha-synucleinopathy. Chung CY, Koprich JB, Siddiqi H, Isacson O. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009 29:3365-73. [PubMed:19295143] [PMC:PMC2693917]

Hypoxia-inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1. Gimm T, Wiese M, Teschemacher B, Deggerich A, Schdel J, Knaup KX, Hackenbeck T, Hellerbrand C, Amann K, Wiesener MS, Hning S, Eckardt KU, Warnecke C. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2010 24:4443-58. (WB, ChrIP; Human) [PubMed:20624928]

IFN- attenuates hypoxia-inducible factor (HIF) activity in intestinal epithelial cells through transcriptional repression of HIF-1. Glover LE, Irizarry K, Scully M, Campbell EL, Bowers BE, Aherne CM, Kominsky DJ, MacManus CF, Colgan SP. Journal of immunology (Baltimore, Md. : 1950). 2011 186:1790-8. [PubMed:21199896]

Hypoxia inducible factor 1 links fast-patterned muscle activity and fast muscle phenotype in rats. Lunde IG, Anton SL, Bruusgaard JC, Rana ZA, Ellefsen S, Gundersen K. The Journal of physiology. 2011 589:1443-54. (WB; Human, Rat) [PubMed:21262877] [PMC:PMC3082102]

Hypoxia-inducible factor 2 (HIF-2) heterozygous-null mice exhibit exaggerated carotid body sensitivity to hypoxia, breathing instability, and hypertension. Peng YJ, Nanduri J, Khan SA, Yuan G, Wang N, Kinsman B, Vaddi DR, Kumar GK, Garcia JA, Semenza GL, Prabhakar NR. Proceedings of the National Academy of Sciences of the United States of America. 2011 108:3065-70. [PubMed:21288809] [PMC:PMC3041114]

High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq. Schdel J, Oikonomopoulos S, Ragoussis J, Pugh CW, Ratcliffe PJ, Mole DR. Blood. 2011 117:e207-17. [PubMed:21447827] [PMC:PMC3374576]

Differential hypoxic regulation of hypoxia-inducible factors 1alpha and 2alpha. Lin Q, Cong X, Yun Z. Molecular cancer research : MCR. 2011 9:757-65. (WB; Human) [PubMed:21571835] [PMC:PMC3117969]

Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Luo W, Hu H, Chang R, Zhong J, Knabel M, O'Meally R, Cole RN, Pandey A, Semenza GL. Cell. 2011 145:732-44. (WB, ChrIP; Human) [PubMed:21620138] [PMC:PMC3130564]

Aryl hydrocarbon receptor and aryl hydrocarbon nuclear translocator expression in human and rat placentas and transcription activity in human trophoblast cultures. Stejskalova L, Vecerova L, Perz LM, Vrzal R, Dvorak Z, Nachtigal P, Pavek P. Toxicological sciences : an official journal of the Society of Toxicology. 2011 123:26-36. (IHC; Human, Rat) [PubMed:21666223]

Toll-like receptor activation and hypoxia use distinct signaling pathways to stabilize hypoxia-inducible factor 1 (HIF1A) and result in differential HIF1A-dependent gene expression. Jantsch J, Wiese M, Schdel J, Castiglione K, Glsner J, Kolbe S, Mole D, Schleicher U, Eckardt KU, Hensel M, Lang R, Bogdan C, Schnare M, Willam C. Journal of leukocyte biology. 2011 90:551-62. [PubMed:21685248]

Hypoxia-inducible factor-1 drives annexin A2 system-mediated perivascular fibrin clearance in oxygen-induced retinopathy in mice. Huang B, Deora AB, He KL, Chen K, Sui G, Jacovina AT, Almeida D, Hong P, Burgman P, Hajjar KA. Blood. 2011 118:2918-29. [PubMed:21788340] [PMC:PMC3172807]

Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation. Wong CC, Gilkes DM, Zhang H, Chen J, Wei H, Chaturvedi P, Fraley SI, Wong CM, Khoo US, Ng IO, Wirtz D, Semenza GL. Proceedings of the National Academy of Sciences of the United States of America. 2011 108:16369-74. (IHC, WB, IHC-P; Mouse, Human) [PubMed:21911388] [PMC:PMC3182724]

The von Hippel-Lindau tumor suppressor protein promotes c-Cbl-independent poly-ubiquitylation and degradation of the activated EGFR. Zhou L, Yang H. PloS one. 2011 6:e23936. [PubMed:21949687] [PMC:PMC3174936]

Depolarized MUC1 expression is closely associated with hypoxic markers and poor outcome in resected non-small cell lung cancer. Kaira K, Nakagawa K, Ohde Y, Okumura T, Takahashi T, Murakami H, Endo M, Kondo H, Nakajima T, Yamamoto N. International journal of surgical pathology. 2012 20:223-32. (IHC; Human) [PubMed:22108499]

HIF2-Sp1 interaction mediates a deacetylation-dependent FVII-gene activation under hypoxic conditions in ovarian cancer cells. Koizume S, Ito S, Miyagi E, Hirahara F, Nakamura Y, Sakuma Y, Osaka H, Takano Y, Ruf W, Miyagi Y. Nucleic acids research. 2012 40:5389-401. (WB, ChrIP; Human) [PubMed:22402494] [PMC:PMC3384323]

Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression. Schdel J, Bardella C, Sciesielski LK, Brown JM, Pugh CW, Buckle V, Tomlinson IP, Ratcliffe PJ, Mole DR. Nature genetics. 2012 44:420-5, S1-2. (ChrIP; Human) [PubMed:22406644] [PMC:PMC3378637]

An oxygen-regulated switch in the protein synthesis machinery. Uniacke J, Holterman CE, Lachance G, Franovic A, Jacob MD, Fabian MR, Payette J, Holcik M, Pause A, Lee S. Nature. 2012 486:126-9. (WB; Human) [PubMed:22678294]

Intracellular pathogen Leishmania donovani activates hypoxia inducible factor-1 by dual mechanism for survival advantage within macrophage. Singh AK, Mukhopadhyay C, Biswas S, Singh VK, Mukhopadhyay CK. PloS one. 2012 7:e38489. (WB; Mouse) [PubMed:22701652] [PMC:PMC3373497]

High-resolution genome-wide mapping of AHR and ARNT binding sites by ChIP-Seq. Lo R, Matthews J. Toxicological sciences : an official journal of the Society of Toxicology. 2012 130:349-61. (ChrIP; Human) [PubMed:22903824]

The requirement of c-Jun N-terminal kinase 2 in regulation of hypoxia-inducing factor-1 mRNA stability. Zhang D, Li J, Zhang M, Gao G, Zuo Z, Yu Y, Zhu L, Gao J, Huang C. The Journal of biological chemistry. 2012 287:34361-71. (WB; Mouse) [PubMed:22910906] [PMC:PMC3464542]

Cell-specific regulation of Ferroportin transcription following experimentally-induced acute anemia in mice. Chiabrando D, Fiorito V, Marro S, Silengo L, Altruda F, Tolosano E. Blood cells, molecules & diseases. 2013 50:25-30. (WB, IP; Human) [PubMed:22921471]

Hypoxia regulates CD44 and its variant isoforms through HIF-1 in triple negative breast cancer. Krishnamachary B, Penet MF, Nimmagadda S, Mironchik Y, Raman V, Solaiyappan M, Semenza GL, Pomper MG, Bhujwalla ZM. PloS one. 2012 7:e44078. (WB; Human) [PubMed:22937154] [PMC:PMC3429433]

Upstream stimulatory factor 2 and hypoxia-inducible factor 2 (HIF2) cooperatively activate HIF2 target genes during hypoxia. Pawlus MR, Wang L, Ware K, Hu CJ. Molecular and cellular biology. 2012 32:4595-610. (WB, ChrIP; Human) [PubMed:22966206] [PMC:PMC3486188]

Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor B promotes lymphatic metastasis of hypoxic breast cancer cells. Schito L, Rey S, Tafani M, Zhang H, Wong CC, Russo A, Russo MA, Semenza GL. Proceedings of the National Academy of Sciences of the United States of America. 2012 109:E2707-16. (ChrIP; Human) [PubMed:23012449] [PMC:PMC3479586]

Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression. Luo W, Chang R, Zhong J, Pandey A, Semenza GL. Proceedings of the National Academy of Sciences of the United States of America. 2012 109:E3367-76. (ChrIP; Human) [PubMed:23129632] [PMC:PMC3523832]

Hypoxia-inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. Chaturvedi P, Gilkes DM, Wong CC, Luo W, Zhang H, Wei H, Takano N, Schito L, Levchenko A, Semenza GL. The Journal of clinical investigation. 2013 123:189-205. (WB, ChrIP; Human) [PubMed:23318994] [PMC:PMC3533298]

Effect of Combined Perftoran and Indocyanine Green-Photodynamic Therapy on HypoxamiRs and OncomiRs in Lung Cancer Cells. Amira M Gamal-Eldeen, Amani A Alrehaili, Afaf Alharthi, Bassem M Raafat. Frontiers in pharmacology. 2022 April;13:844104. [Full Text Article] [PubMed:35370727] [PMC:PMC8966667]

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Gene Name:	aryl hydrocarbon receptor nuclear translocator
Synonyms:	ARNT, ARNT protein, BHLHe2, HIF-1beta, HIF1-beta, HIF1BETA, TANGO, HIF-1-beta, HIF1B
Target Sequences:	NM_001668 NP_001659.1 P27540

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ARNT / HIF-1-Beta

aryl hydrocarbon receptor nuclear translocator

Publications (64)

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