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A Review of Post-translational Modifications and Subcellular Localization of Ets Transcription Factors: Possible Connection with Cancer and Involvement in the Hypoxic Response

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Transcription Factors

Part of the book series: Methods in Molecular Biology ((MIMB,volume 647))

Abstract

Post-translational modifications and subcellular localizations modulate transcription factors, generating a code that is deciphered into an activity. We describe our current understanding of these processes for Ets factors, which have recently been recognized for their importance in various biological processes. We present the global picture for the family, and then focus on particular aspects related to cancer and hypoxia. The analysis of Post-translational modification and cellular localization is only beginning to enter the age of “omic,” high content, systems biology. Our snap-shots of particularly active fields point to the directions in which new techniques will be needed, in our search for a more complete description of regulatory pathways.

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References

  1. Buchwalter G, Gross C, Wasylyk B (2004) Ets ternary complex transcription factors. Gene 324:1–14

    Article  PubMed  CAS  Google Scholar 

  2. Oikawa T, Yamada T (2003) Molecular biology of the Ets family of transcription factors. Gene 303:11–34

    Article  PubMed  CAS  Google Scholar 

  3. Seth A, Watson DK (2005) Ets transcription factors and their emerging roles in human cancer. Eur J Cancer 41:2462–2478

    Article  PubMed  CAS  Google Scholar 

  4. Tootle TL, Rebay I (2005) Post-translational modifications influence transcription factor activity: a view from the ETS superfamily. Bioessays 27:285–298

    Article  PubMed  CAS  Google Scholar 

  5. Whitmarsh AJ, Davis RJ (2000) Regulation of transcription factor function by phosphorylation. Cell Mol Life Sci 57:1172–1183

    Article  PubMed  CAS  Google Scholar 

  6. Slawson C, Housley MP, Hart GW (2006) O-GlcNAc cycling: how a single sugar post-translational modification is changing the way we think about signaling networks. J Cell Biochem 97:71–83

    Article  PubMed  CAS  Google Scholar 

  7. Sadoul K, Boyault C, Pabion M, Khochbin S (2008) Regulation of protein turnover by acetyltransferases and deacetylases. Biochimie 90:306–312

    Article  PubMed  CAS  Google Scholar 

  8. Thompson SJ, Loftus LT, Ashley MD, Meller R (2008) Ubiquitin-proteasome system as a modulator of cell fate. Curr Opin Pharmacol 8:90–95

    Article  PubMed  CAS  Google Scholar 

  9. Lyst MJ, Stancheva I (2007) A role for SUMO modification in transcriptional repression and activation. Biochem Soc Trans 35:1389–1392

    Article  PubMed  CAS  Google Scholar 

  10. Janknecht R, Ernst WH, Pingoud V, Nordheim A (1993) Activation of ternary complex factor Elk-1 by MAP kinases. EMBO J 12:5097–5104

    PubMed  CAS  Google Scholar 

  11. Gille H, Strahl T, Shaw PE (1995) Activation of ternary complex factor Elk-1 by stress-activated protein kinases. Curr Biol 5:1191–1200

    Article  PubMed  CAS  Google Scholar 

  12. Shaw PE, Saxton J (2003) Ternary complex factors: prime nuclear targets for mitogen-activated protein kinases. Int J Biochem Cell Biol 35:1210–1226

    Article  PubMed  CAS  Google Scholar 

  13. Yang SH, Jaffray E, Hay RT, Sharrocks AD (2003) Dynamic interplay of the SUMO and ERK pathways in regulating ELK-1 transcription activity. Mol Cell 12:63–74

    Article  PubMed  CAS  Google Scholar 

  14. Salinas S, Briancon-Marjollet A, Bossis G, Lopez MA, Piechaczyk M, Jariel-Encontre I, Debant A, Hipskind RA (2004) SUMOylation regulates nucleo-cytoplasmic shuttling of Elk-1. J Cell Biol 165:767–773

    Article  PubMed  CAS  Google Scholar 

  15. Giovane A, Pintzas A, Maira SM, Sobieszczuk P, Wasylyk B (1994) Net, a new Ets transcription factor that is activated by Ras. Genes Dev 8:1502–1513

    Article  PubMed  CAS  Google Scholar 

  16. Ducret C, Maira SM, Lutz Y, Wasylyk B (2000) The ternary complex factor Net contains two distinct elements that mediate different responses to MAP kinase signalling cascades. Oncogene 19:5063–5072

    Article  PubMed  CAS  Google Scholar 

  17. Wasylyk C, Zheng H, Castell C, Debussche L, Multon MC, Wasylyk B (2008) Inhibition of the Ras-Net (Elk-3) pathway by a novel pyrazole that affects microtubules. Cancer Res 68:1275–1283

    Article  PubMed  CAS  Google Scholar 

  18. Ducret C, Maira SM, Dierich A, Wasylyk B (1999) The net repressor is regulated by nuclear export in response to anisomycin, UV, and heat shock. Mol Cell Biol 19:7076–7087

    PubMed  CAS  Google Scholar 

  19. Wasylyk C, Criqui-Filipe P, Wasylyk B (2005) Sumoylation of the net inhibitory domain (NID) is stimulated by PIAS1 and has a negative effect on the transcriptional activity of Net. Oncogene 24:820–828

    Article  PubMed  CAS  Google Scholar 

  20. Gross C, Buchwalter G, Dubois-Pot H, Cler E, Zheng H, Wasylyk B (2007) The ternary complex factor net is downregulated by hypoxia and regulates hypoxia-responsive genes. Mol Cell Biol 27:4133–4141

    Article  PubMed  CAS  Google Scholar 

  21. Strahl T, Gille H, Shaw PE (1996) Selective response of ternary complex factor Sap1a to different mitogen-activated protein kinase subgroups. Proc Natl Acad Sci USA 93:11563–11568

    Article  PubMed  CAS  Google Scholar 

  22. Maki K, Arai H, Waga K, Sasaki K, Nakamura F, Imai Y, Kurokawa M, Hirai H, Mitani K (2004) Leukemia-related transcription factor TEL is negatively regulated through extracellular signal-regulated kinase-induced phosphorylation. Mol Cell Biol 24:3227–3237

    Article  PubMed  CAS  Google Scholar 

  23. Arai H, Maki K, Waga K, Sasaki K, Nakamura Y, Imai Y, Kurokawa M, Hirai H, Mitani K (2002) Functional regulation of TEL by p38-induced phosphorylation. Biochem Biophys Res Commun 299:116–125

    Article  PubMed  CAS  Google Scholar 

  24. Hanson CA, Wood LD, Hiebert SW (2008) Cellular stress triggers TEL nuclear export via two genetically separable pathways. J Cell Biochem 104:488–498

    Article  PubMed  CAS  Google Scholar 

  25. Roukens MG, Alloul-Ramdhani M, Vertegaal AC, Anvarian Z, Balog CI, Deelder AM, Hensbergen PJ, Baker DA (2008) Identification of a new site of sumoylation on Tel (ETV6) uncovers a PIAS-dependent mode of regulating Tel function. Mol Cell Biol 28:2342–2357

    Article  PubMed  CAS  Google Scholar 

  26. Roukens MG, Alloul-Ramdhani M, Moghadasi S, Op den Brouw M, Baker DA (2008) Downregulation of vertebrate Tel (ETV6) and Drosophila Yan is facilitated by an evolutionarily conserved mechanism of F-box-mediated ubiquitination. Mol Cell Biol 28:4394–4406

    Article  PubMed  CAS  Google Scholar 

  27. Yang BS, Hauser CA, Henkel G, Colman MS, Van Beveren C, Stacey KJ, Hume DA, Maki RA, Ostrowski MC (1996) Ras-mediated phosphorylation of a conserved thronine residue enhances the transactivation activities of c-Ets1 and c-Ets2. Mol Cell Biol 16:538–547

    PubMed  CAS  Google Scholar 

  28. Wasylyk C, Bradford AP, Gutierrez-Hartmann A, Wasylyk B (1997) Conserved mechanisms of Ras regulation of evolutionary related transcription factors, Ets2 and Pointed P2. Oncogene 14:899–913

    Article  PubMed  CAS  Google Scholar 

  29. Lindemann RK, Braig M, Ballschmieter P, Guise TA, Nordheim A, Dittmer J (2003) Protein kinase Calpha regulates Ets1 transcriptional activity in invasive breast cancer cells. Int J Oncol 22:799–805

    PubMed  CAS  Google Scholar 

  30. Cowley DO, Graves BJ (2000) Phosphorylation represses Ets-1 DNA binding by reinforcing autoinhibition. Genes Dev 14:366–376

    PubMed  CAS  Google Scholar 

  31. Liu H, Grundstrom T (2002) Calcium regulation of GM-CSF by calmodulin-dependent kinase II phosphorylation of Ets1. Mol Biol Cell 13:4497–4507

    Article  PubMed  CAS  Google Scholar 

  32. Czuwara-Ladykowska J, Sementchenko VI, Watson DK, Trojanowska M (2002) Ets1 is an effector of the transforming growth factor-beta (TGF-geta) signaling pathway and an antagonist of the profibrotic effects of TGF-beta. J Biol Chem 277:20399–20408

    Article  PubMed  CAS  Google Scholar 

  33. Ji Z, Degerny C, Vintonenko N, Deheuninck J, Foveau B, Leroy C, Coll J, Tulasne D, Baert JL, Fafeur V (2007) Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation. Oncogene 26:395–406

    Article  PubMed  CAS  Google Scholar 

  34. Fujiwara S, Fisher RJ, Bhat NK, Diaz de la Espina SM, Papas TS (1988) A short-lived nuclear phosphoprotein encoded by the human Ets-2 proto-oncogene is stabilized by activation of protein kinase C. Mol Cell Biol 8:4700–4706

    PubMed  CAS  Google Scholar 

  35. O’Hagan RC, Tozer RG, Symons M, McCormick F, Hassell JA (1996) The activity of the Ets transcription factor PEA3 is regulated by two distinct MAPK cascades. Oncogene 13:1323–1333

    PubMed  Google Scholar 

  36. Bojovic BB, Hassell JA (2008) The transactivation function of the Pea3 subfamily Ets transcription factors is regulated by sumoylation. DNA Cell Biol 27:289–305

    Article  PubMed  CAS  Google Scholar 

  37. Baert JL, Beaudoin C, Coutte L, de Launoit Y (2002) ERM transactivation is up-regulated by the repression of DNA binding after the PKA phosphorylation of a consensus site at the edge of the ETS domain. J Biol Chem 277:1002–1012

    Article  PubMed  CAS  Google Scholar 

  38. Janknecht R, Monte D, Baert JL, de Launoit Y (1996) The ETS-related transcription factor ERM is a nuclear target of signaling cascades involving MAPK and PKA. Oncogene 13:1745–1754

    PubMed  CAS  Google Scholar 

  39. Degerny C, de Launoit Y, Baert JL (2008) ERM transcription factor contains an inhibitory domain which functions in sumoylation-dependent manner. Biochim Biophys Acta 1779:183–194

    Article  PubMed  CAS  Google Scholar 

  40. Baert JL, Beaudoin C, Monte D, Degerny C, Mauen S, de Launoit Y (2007) The 26S proteasome system degrades the ERM transcription factor and regulates its transcription-enhancing activity. Oncogene 26:415–424

    Article  PubMed  CAS  Google Scholar 

  41. Wu J, Janknecht R (2002) Regulation of the ETS transcription factor ER81 by the 90-kDa ribosomal S6 kinase 1 and protein kinase A. J Biol Chem 277:42669–42679

    Article  PubMed  CAS  Google Scholar 

  42. Janknecht R (2003) Regulation of the ER81 transcription factor and its coactivators by mitogen- and stress-activated protein kinase 1 (MSK1). Oncogene 22:746–755

    Article  PubMed  CAS  Google Scholar 

  43. Janknecht R (2001) Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase 2. J Biol Chem 276:41856–41861

    Article  PubMed  CAS  Google Scholar 

  44. Goel A, Janknecht R (2003) Acetylation-mediated transcriptional activation of the ETS protein ER81 by p300, P/CAF, and HER2/Neu. Mol Cell Biol 23:6243–6254

    Article  PubMed  CAS  Google Scholar 

  45. Juang YT, Solomou EE, Rellahan B, Tsokos GC (2002) Phosphorylation and O-linked glycosylation of Elf-1 leads to its translocation to the nucleus and binding to the promoter of the TCRι-chain. J Immunol 168:2865–2871

    PubMed  CAS  Google Scholar 

  46. Miyazaki Y, Boccuni P, Mao S, Zhang J, Erdjument-Bromage H, Tempst P, Kiyokawa H, Nimer SD (2001) Cyclin A-dependent phosphorylation of the ETS-related protein, MEF, restricts its activity to the G1 phase of the cell cycle. J Biol Chem 276:40528–40536

    Article  PubMed  CAS  Google Scholar 

  47. Liu Y, Hedvat CV, Mao S, Zhu XH, Yao J, Nguyen H, Koff A, Nimer SD (2006) The ETS protein MEF is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCFSkp2. Mol Cell Biol 26:3114–3123

    Article  PubMed  CAS  Google Scholar 

  48. Suico MA, Nakamura H, Lu Z, Saitoh H, Shuto T, Nakao M, Kai H (2006) SUMO down-regulates the activity of Elf4/myeloid Elf-1-like factor. Biochem Biophys Res Commun 348:880–888

    Article  PubMed  CAS  Google Scholar 

  49. Zhang XK, Watson DK (2005) The FLI-1 transcription factor is a short-lived phosphoprotein in T cells. J Biochem 137:297–302

    Article  PubMed  CAS  Google Scholar 

  50. van den Akker E, Ano S, Shih HM, Wang LC, Pironin M, Palvimo JJ, Kotaja N, Kirsh O, Dejean A, Ghysdael J (2005) FLI-1 functionally interacts with PIASxα a member of the PIAS E3 SUMO ligase family. J Biol Chem 280:38035–38046

    Article  PubMed  CAS  Google Scholar 

  51. Murakami K, Mavrothalassitis G, Bhat NK, Fisher RJ, Papas TS (1993) Human ERG-2 protein is a phosphorylated DNA-binding protein-a distinct member of the Ets family. Oncogene 8:1559–1566

    PubMed  CAS  Google Scholar 

  52. Pongubala JM, Van Beveren C, Nagulapalli S, Klemsz MJ, McKercher SR, Maki RA, Atchison ML (1993) Effect of PU.1 phosphorylation on interaction with NF-EM5 and transcriptional activation. Science 259:1622–1625

    Article  PubMed  CAS  Google Scholar 

  53. Wang JM, Lai MZ, Yang-Yen HF (2003) Interleukin-3 stimulation of mcl-1 gene transcription involves activation of the PU.1 transcription factor through a p38 mitogen-activated protein kinase-dependent pathway. Mol Cell Biol 23:1896–1909

    Article  PubMed  CAS  Google Scholar 

  54. Mao C, Ray-Gallet D, Tavitian A, Moreau-Gachelin F (1996) Differential phosphorylations of Spi-B and Spi-1 transcription factors. Oncogene 12:863–873

    PubMed  CAS  Google Scholar 

  55. Ray-Gallet D, Moreau-Gachelin F (1999) Phosphorylation of the Spi-B transcription factor reduces its intrinsic stability. FEBS Lett 464:164–168

    Article  PubMed  CAS  Google Scholar 

  56. Sgouras DN, Athanasiou MA, Beal GJ Jr, Fisher RJ, Blair DG, Mavrothalassitis GJ (1995) ERF: an ETS domain protein with strong transcriptional repressor activity, can suppress Ets-associated tumorigenesis and is regulated by phosphorylation during cell cycle and mitogenic stimulation. EMBO J 14:4781–4793

    PubMed  CAS  Google Scholar 

  57. Le Gallic L, Sgouras D, Beal G Jr, Mavrothalassitis G (1999) Transcriptional repressor ERF is a Ras/mitogen-activated protein kinase target that regulates cellular proliferation. Mol Cell Biol 19:4121–4133

    PubMed  Google Scholar 

  58. Le Gallic L, Virgilio L, Cohen P, Biteau B, Mavrothalassitis G (2004) ERF nuclear shuttling, a continuous monitor of ERK activity that links it to cell cycle progression. Mol Cell Biol 24:1206–1218

    Article  PubMed  CAS  Google Scholar 

  59. Hoffmeyer A, Avots A, Flory E, Weber CK, Serfling E, Rapp UR (1998) The GABP-responsive element of the interleukin-2 enhancer is regulated by JNK/SAPK-activating pathways in T lymphocytes. J Biol Chem 273:10112–10119

    Article  PubMed  CAS  Google Scholar 

  60. Sunesen M, Huchet-Dymanus M, Christensen MO, Changeux JP (2003) Phosphorylation-elicited quaternary changes of GA binding protein in transcriptional activation. Mol Cell Biol 23:8008–8018

    Article  PubMed  CAS  Google Scholar 

  61. Rosmarin AG, Resendes KK, Yang Z, McMillan JN, Fleming SL (2004) GA-binding protein transcription factor: a review of GABP as an integrator of intracellular signaling and protein–protein interactions. Blood Cells Mol Dis 32:143–154

    Article  PubMed  CAS  Google Scholar 

  62. Chakrabarti SR, Sood R, Nandi S, Nucifora G (2000) Post-translational modification of TEL and TEL/AML1 by SUMO-1 and cell-cycle-dependent assembly into nuclear bodies. Proc Natl Acad Sci USA 97:13281–13285

    Article  PubMed  CAS  Google Scholar 

  63. Sumarsono SH, Wilson TJ, Tymms MJ, Venter DJ, Corrick CM, Kola R, Lahoud MH, Papas TS, Seth A, Kola I (1996) Down’s syndrome-like skeletal abnormalities in Ets2 transgenic mice. Nature 379:534–537

    Article  PubMed  CAS  Google Scholar 

  64. Papas TS, Watson DK, Sacchi N, Fujiwara S, Seth AK, Fisher RJ, Bhat NK, Mavrothalassitis G, Koizumi S, Jorcyk CL et al (1990) ETS family of genes in leukemia and Down syndrome. Am J Med Genet Suppl 7:251–261

    PubMed  CAS  Google Scholar 

  65. Dooley S, Herlitzka I, Hanselmann R, Ermis A, Henn W, Remberger K, Hopf T, Welter C (1996) Constitutive expression of c-fos and c-jun, overexpression of Ets-2, and reduced expression of metastasis suppressor gene mm23-H1 in rheumatoid arthritis. Ann Rheum Dis 55:298–304

    Article  PubMed  CAS  Google Scholar 

  66. Tsokos GC, Nambiar MP, Juang YT (2003) Activation of the Ets transcription factor Elf-1 requires phosphorylation and glycosylation: defective expression of activated Elf-1 is involved in the decreased TCR zeta chain gene expression in patients with systemic lupus erythematosus. Ann N Y Acad Sci 987:240–245

    Article  PubMed  CAS  Google Scholar 

  67. Muller JM, Krauss B, Kaltschmidt C, Baeuerle PA, Rupec RA (1997) Hypoxia induces c-fos transcription via a mitogen-activated protein kinase-dependent pathway. J Biol Chem 272:23435–23439

    Article  PubMed  CAS  Google Scholar 

  68. Valjent E, Pages C, Rogard M, Besson MJ, Maldonado R, Caboche J (2001) Delta 9-tetrahydrocannabinol-induced MAPK/ERK and Elk-1 activation in vivo depends on dopaminergic transmission. Eur J Neurosci 14:342–352

    Article  PubMed  CAS  Google Scholar 

  69. Valjent E, Corvol JC, Pages C, Besson MJ, Maldonado R, Caboche J (2000) Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties. J Neurosci 20:8701–8709

    PubMed  CAS  Google Scholar 

  70. van Riggelen J, Buchwalter G, Soto U, De-Castro Arce J, Hausen HZ, Wasylyk B, Rosl F (2005) Loss of net as repressor leads to constitutive increased c-fos transcription in cervical cancer cells. J Biol Chem 280:3286–3294

    Article  PubMed  CAS  Google Scholar 

  71. Zheng H, Wasylyk C, Ayadi A, Abecassis J, Schalken JA, Rogatsch H, Wernert N, Maira SM, Multon MC, Wasylyk B (2003) The transcription factor Net regulates the angiogenic switch. Genes Dev 17:2283–2297

    Article  PubMed  CAS  Google Scholar 

  72. Hsu T, Trojanowska M, Watson DK (2004) Ets proteins in biological control and cancer. J Cell Biochem 91:896–903

    Article  PubMed  CAS  Google Scholar 

  73. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  PubMed  CAS  Google Scholar 

  74. Sementchenko VI, Watson DK (2000) Ets target genes: past, present and future. Oncogene 19:6533–6548

    Article  PubMed  CAS  Google Scholar 

  75. Nakayama T, Ito M, Ohtsuru A, Naito S, Nakashima M, Sekine I (1999) Expression of the Ets-1 proto-oncogene in human thyroid tumor. Mod Pathol 12:61–68

    PubMed  CAS  Google Scholar 

  76. He J, Pan Y, Hu J, Albarracin C, Wu Y, Dai JL (2007) Profile of Ets gene expression in human breast carcinoma. Cancer Biol Ther 6:76–82

    Article  PubMed  CAS  Google Scholar 

  77. Stanbridge EJ, Flandermeyer RR, Daniels DW, Nelson-Rees WA (1981) Specific chromosome loss associated with the expression of tumorigenicity in human cell hybrids. Somatic Cell Genet 7:699–712

    Article  PubMed  CAS  Google Scholar 

  78. Milde-Langosch K (2005) The Fos family of transcription factors and their role in tumourigenesis. Eur J Cancer 41:2449–2461

    Article  PubMed  CAS  Google Scholar 

  79. Li B, Ni P, Zhu Q, Cao H, Xu H, Zhang S, Au C, Zhang Y (2008) Growth inhibitory effect of the ternary complex factor Net on human pancreatic carcinoma cell lines. Tohoku J Exp Med 216:139–147

    Article  PubMed  CAS  Google Scholar 

  80. Bos JL (1989) ras oncogenes in human cancer: a review. Cancer Res 49:4682–4689

    PubMed  CAS  Google Scholar 

  81. Treisman R (1994) Ternary complex factors: growth factor regulated transcriptional activators. Curr Opin Genet Dev 4:96–101

    Article  PubMed  CAS  Google Scholar 

  82. Tsujimoto H, Nishizuka S, Redpath JL, Stanbridge EJ (1999) Differential gene expression in tumorigenic and nontumorigenic HeLa × normal human fibroblast hybrid cells. Mol Carcinog 26:298–304

    Article  PubMed  CAS  Google Scholar 

  83. Benbrahim-Tallaa L, Webber MM, Waalkes MP (2007) Mechanisms of acquired androgen independence during arsenic-induced malignant transformation of human prostate epithelial cells. Environ Health Perspect 115:243–247

    Article  PubMed  CAS  Google Scholar 

  84. Libermann TA, Zerbini LF (2006) Targeting transcription factors for cancer gene therapy. Curr Gene Ther 6:17–33

    Article  PubMed  CAS  Google Scholar 

  85. Nakae K, Nakajima K, Inazawa J, Kitaoka T, Hirano T (1995) ERM, a PEA3 subfamily of Ets transcription factors, can cooperate with c-Jun. J Biol Chem 270:23795–23800

    Article  PubMed  CAS  Google Scholar 

  86. Oikawa T (2004) ETS transcription factors: possible targets for cancer therapy. Cancer Sci 95:626–633

    Article  PubMed  CAS  Google Scholar 

  87. Span PN, Manders P, Heuvel JJ, Thomas CM, Bosch RR, Beex LV, Sweep CG (2002) Expression of the transcription factor Ets-1 is an independent prognostic marker for relapse-free survival in breast cancer. Oncogene 21:8506–8509

    Article  PubMed  CAS  Google Scholar 

  88. Ying TH, Hsieh YH, Hsieh YS, Liu JY (2008) Antisense oligonucleotide Elk-1 suppresses the tumorigenicity of human hepatocellular carcinoma cells. Cell Biol Int 32:210–216

    Article  PubMed  Google Scholar 

  89. Brahimi-Horn C, Pouyssegur J (2006) The role of the hypoxia-inducible factor in tumor metabolism growth and invasion. Bull Cancer 93:73–80

    Google Scholar 

  90. Pugh CW, Ratcliffe PJ (2003) Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 9:677–684

    Article  PubMed  CAS  Google Scholar 

  91. Schofield CJ, Ratcliffe PJ (2004) Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 5:343–354

    Article  PubMed  CAS  Google Scholar 

  92. Oikawa M, Abe M, Kurosawa H, Hida W, Shirato K, Sato Y (2001) Hypoxia induces transcription factor Ets-1 via the activity of hypoxia-inducible factor-1. Biochem Biophys Res Commun 289:39–43

    Article  PubMed  CAS  Google Scholar 

  93. Manalo DJ, Rowan A, Lavoie T, Natarajan L, Kelly BD, Ye SQ, Garcia JG, Semenza GL (2005) Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. Blood 105:659–669

    Article  PubMed  CAS  Google Scholar 

  94. Miyoshi A, Kitajima Y, Ide T, Ohtaka K, Nagasawa H, Uto Y, Hori H, Miyazaki K (2006) Hypoxia accelerates cancer invasion of hepatoma cells by upregulating MMP expression in an HIF-1-alpha-independent manner. Int J Oncol 29:1533–1539

    PubMed  CAS  Google Scholar 

  95. Christensen RA, Fujikawa K, Madore R, Oettgen P, Varticovski L (2002) NERF2, a member of the Ets family of transcription factors, is increased in response to hypoxia and angiopoietin-1: a potential mechanism for Tie2 regulation during hypoxia. J Cell Biochem 85:505–515

    Article  PubMed  CAS  Google Scholar 

  96. Hu CJ, Sataur A, Wang L, Chen H, Simon MC (2007) The N-terminal transactivation domain confers target gene specificity of hypoxia-inducible factors HIF-1α and HIF-2α. Mol Biol Cell 18:4528–4542

    Article  PubMed  CAS  Google Scholar 

  97. Aprelikova O, Wood M, Tackett S, Chandramouli GV, Barrett JC (2006) Role of Ets transcription factors in the hypoxia-inducible factor-2 target gene selection. Cancer Res 66:5641–5647

    Article  PubMed  CAS  Google Scholar 

  98. Elvert G, Kappel A, Heidenreich R, Englmeier U, Lanz S, Acker T, Rauter M, Plate K, Sieweke M, Breier G, Flamme I (2003) Cooperative interaction of hypoxia-inducible factor-2α (HIF-2α) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). J Biol Chem 278:7520–7530

    Article  PubMed  CAS  Google Scholar 

  99. Ohradanova A, Gradin K, Barathova M, Zatovicova M, Holotnakova T, Kopacek J, Parkkila S, Poellinger L, Pastorekova S, Pastorek J (2008) Hypoxia upregulates expression of human endosialin gene via hypoxia-inducible factor 2. Br J Cancer 99:1348–1356

    Article  PubMed  CAS  Google Scholar 

  100. Le Bras A, Lionneton F, Mattot V, Lelievre E, Caetano B, Spruyt N, Soncin F (2007) HIF-2α specifically activates the VE-cadherin promoter independently of hypoxia and in synergy with Ets-1 through two essential Ets-binding sites. Oncogene 26:7480–7489

    Article  PubMed  CAS  Google Scholar 

  101. Dutta D, Ray S, Vivian JL, Paul S (2008) Activation of the VEGFR1 chromatin domain. J Biol Chem 283:25404–25413

    Article  PubMed  CAS  Google Scholar 

  102. Salnikow K, Aprelikova O, Ivanov S, Tackett S, Kaczmarek M, Karaczyn A, Yee H, Kasprzak KS, Niederhuber J (2008) Regulation of hypoxia-inducible genes by Ets1 transcription factor. Carcinogenesis 29:1493–1499

    Article  PubMed  CAS  Google Scholar 

  103. Ke Q, Costa M (2006) Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol 70:1469–1480

    Article  PubMed  CAS  Google Scholar 

  104. Yan SF, Lu J, Zou YS, Soh-Won J, Cohen DM, Buttrick PM, Cooper DR, Steinberg SF, Mackman N, Pinsky DJ, Stern DM (1999) Hypoxia-associated induction of early growth response-1 gene expression. J Biol Chem 274:15030–15040

    Article  PubMed  CAS  Google Scholar 

  105. Gross C, Dubois-Pot H, Wasylyk B (2008) The ternary complex factor Net/Elk-3 participates in the transcriptional response to hypoxia and regulates HIF-1α. Oncogene 27:1333–1341

    Article  PubMed  CAS  Google Scholar 

  106. Man AK, Young LJ, Tynan JA, Lesperance J, Egeblad M, Werb Z, Hauser CA, Muller WJ, Cardiff RD, Oshima RG (2003) Ets2-dependent stromal regulation of mouse mammary tumors. Mol Cell Biol 23:8614–8625

    Article  PubMed  CAS  Google Scholar 

  107. Ilagan R, Pottratz J, Le K, Zhang L, Wong SG, Ayala R, Iyer M, Wu L, Gambhir SS, Carey M (2006) Imaging mitogen-activated protein kinase function in xenograft models of prostate cancer. Cancer Res 66:10778–10785

    Article  PubMed  CAS  Google Scholar 

  108. Wei G, Guo J, Doseff AI, Kusewitt DF, Man AK, Oshima RG, Ostrowski MC (2004) Activated Ets2 is required for persistent inflammatory responses in the motheaten viable model. J Immunol 173:1374–1379

    PubMed  CAS  Google Scholar 

  109. Sgambato V, Vanhoutte P, Pages C, Rogard M, Hipskind R, Besson MJ, Caboche J (1998) In vivo expression and regulation of Elk-1, a target of the extracellular-regulated kinase signaling pathway, in the adult rat brain. J Neurosci 18:214–226

    PubMed  CAS  Google Scholar 

  110. Vanhoutte P, Barnier JV, Guibert B, Pages C, Besson MJ, Hipskind RA, Caboche J (1999) Glutamate induces phosphorylation of Elk-1 and CREB, along with c-fos activation, via an extracellular signal-regulated kinase-dependent pathway in brain slices. Mol Cell Biol 19:136–146

    PubMed  CAS  Google Scholar 

  111. Choe ES, Wang JQ (2001) Group I metabotropic glutamate receptor activation increases phosphorylation of c-AMP responses element-binding protein, Elk-1 and extracellular signal-regulated kinases in rat dorsal striatum. Brain Res Mol Brain Res 94:75–84

    Article  PubMed  CAS  Google Scholar 

  112. Choe ES, Parelkar NK, Kim JY, Cho HW, Kang HS, Mao L, Wang JQ (2004) The protein phosphatase 1/2A inhibitor odakaic acid increases CREB and Elk-1 phosphorylation and c-fos expression in the rat striatum in vivo. J Neurochem 89:383–390

    Article  PubMed  CAS  Google Scholar 

  113. Choe ES, Wang JQ (2002) CREB and Elk-1 phosphorylation by metabotropic glutamate receptors in striatal neurons. Int J Mol Med 9:3–10

    PubMed  CAS  Google Scholar 

  114. Nuutinen S, Barik J, Jones IW, Wonnacott S (2007) Differential effects of acute and chronic nicotine on Elk-1 in rat hippocampus. NeuroReport 18:121–126

    Article  PubMed  CAS  Google Scholar 

  115. Berman DE, Hazvi S, Rosenblum K, Seger R, Dudai Y (1998) Specific and differential activation of mitogen-activated protein kinase cascades by unfamiliar taste in the insular cortex of the behaving rat. J Neurosci 18:10037–10044

    PubMed  CAS  Google Scholar 

  116. Hsu T, Schulz RA (2000) Sequence and functional properties of Ets genes in the model organism Drosophila. Oncogene 19:6409–6416

    Article  PubMed  CAS  Google Scholar 

  117. Rebay I, Rubin GM (1995) Yan functions as a general inhibitor of differentiation and is negatively regulated by activation of the Ras1/MAPK pathway. Cell 81:857–866

    Article  PubMed  CAS  Google Scholar 

  118. Baker DA, Mille-Baker B, Wainwright SM, Ish-Horowicz D, Dibb NJ (2001) Mae mediates MAP kinase phosphorylation of Ets transcription factors in Drosophila. Nature 411:330–334

    Article  PubMed  CAS  Google Scholar 

  119. Brunner D, Ducker K, Oellers N, Hafen E, Scholz H, Klambt C (1994) The Ets domain protein pointed-P2 is a target of MAP kinase in the sevenless signal transduction pathway. Nature 370:386–389

    Article  PubMed  CAS  Google Scholar 

  120. Hart AH, Reventar R, Bernstein A (2000) Genetic analysis of Ets genes in C. elegans. Oncogene 19:6400–6408

    Article  PubMed  CAS  Google Scholar 

  121. Beitel GJ, Tuck S, Greenwald I, Horvitz HR (1995) The Caenorhabditis elegans gene lin-1 encodes an Ets-domain protein and defines a branch of the vulval induction pathway. Genes Dev 9:3149–3162

    Article  PubMed  CAS  Google Scholar 

  122. Tan PB, Lackner MR, Kim SK (1998) MAP kinase signaling specificity mediated by the LIN_1 Ets/LIN-31 WH transcription factor complex during C. elegans vulval induction. Cell 93:569–580

    Article  PubMed  CAS  Google Scholar 

  123. Tiensuu T, Larsen MK, Vernersson E, Tuck S (2005) Lin-1 has both positive and negative functions in specifying multiple cell fates induced by Ras/MAP kinase signaling in C. elegans. Dev Biol 286:338–351

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank Christophe Bleunven, Jan Brants, and Catherine Fromental for critical reading of the review. We would like to thank, for fellowships: INCa (DKFZ-CGE project) for Céline Charlot; the Ministère de l’Enseignement Supérieur et de la Recherche for Hélène Dubois-Pot; the Région Alsace (DKFZ-CGE project) for Tsvetan Serchov; and AICR (05-390) and PRIMA (#504587) for Yves Tourrette. We would like to thank for financial support the Ligue Nationale Française contre le Cancer, the Ligue Régionale (Bas-Rhin) contre le Cancer and the Ligue Régionale (Haut-Rhin) contre le Cancer, the Association pour la Recherche contre le Cancer, the Centre National de la Recherche Scientifique, the Institut National de la Santé et de la Recherche Médicale, the EU (FP6 Prima project #504587), INCa (the Axe IV and DKFZ-CGE projects), and AICR (05-390).

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  1. Department of Cancer Biology, Institute de Genetique et de Biologie, Moleculaire et Cellulaire, Lille, France

    Céline Charlot, Hélène Dubois-Pot, Tsvetan Serchov, Yves Tourrette & Bohdan Wasylyk

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  1. Céline Charlot
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  2. Hélène Dubois-Pot
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  3. Tsvetan Serchov
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  4. Yves Tourrette
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  5. Bohdan Wasylyk
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Correspondence to Bohdan Wasylyk .

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  1. Ctr. Cell Biology & Cancer Research, Albany Medical College, New Scotland Ave. 47, Albany, 12208, New York, USA

    Paul J. Higgins

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Charlot, C., Dubois-Pot, H., Serchov, T., Tourrette, Y., Wasylyk, B. (2010). A Review of Post-translational Modifications and Subcellular Localization of Ets Transcription Factors: Possible Connection with Cancer and Involvement in the Hypoxic Response. In: Higgins, P. (eds) Transcription Factors. Methods in Molecular Biology, vol 647. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-738-9_1

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  • DOI: https://doi.org/10.1007/978-1-60761-738-9_1

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