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Regulation of Signal Transduction by DJ-1

  • Stephanie E. Oh
  • M. Maral MouradianEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1037)

Abstract

The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson’s disease.

DJ-1 plays a major role in various pathways. It mediates cell survival and proliferation by activating the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway. It attenuates cell death signaling by inhibiting apoptosis signal-regulating kinase 1 (ASK1) activation as well as by inhibiting mitogen-activated protein kinase kinase kinase 1 (MEKK1/MAP3K1) activation of downstream apoptotic cascades. It also modulates autophagy through the ERK, Akt, or the JNK/Beclin1 pathways. In addition, DJ-1 regulates the transcription of genes essential for male reproductive function, such as spermatogenesis, by relaying nuclear receptor androgen receptor (AR) signaling. In this chapter, we summarize the ways that DJ-1 regulates these pathways, focusing on how its role in signal transduction contributes to cellular homeostasis and the pathologic states that result from dysregulation.

Keywords

DJ-1 Signal transduction Cell signaling MAPK ERK MEK Ras Raf PI3K Akt mTOR MAPK ASK1 Daxx Trx1 JNK p38 MEKK1 AR 

References

  1. Abou-Sleiman PM et al (2003) The role of pathogenic DJ-1 mutations in Parkinson’s disease. Ann Neurol 54(3):283–286PubMedCrossRefGoogle Scholar
  2. Abraham D et al (2000) Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation. J Biol Chem 275(29):22300–22304PubMedCrossRefGoogle Scholar
  3. Adams DG et al (2005) Positive regulation of Raf1-MEK1/2-ERK1/2 signaling by protein serine/threonine phosphatase 2A holoenzymes. J Biol Chem 280(52):42644–42654PubMedCrossRefGoogle Scholar
  4. Alessi DR et al (1995) Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines. Current Biology 5(3):283–295PubMedCrossRefGoogle Scholar
  5. Aleyasin H et al (2010) DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway. Proc Natl Acad Sci U S A 107(7):3186–3191PubMedPubMedCentralCrossRefGoogle Scholar
  6. Andjelkovic M et al (1996) Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors. Proc Natl Acad Sci U S A 93(12):5699–5704PubMedPubMedCentralCrossRefGoogle Scholar
  7. Aron L et al (2010) Pro-survival role for Parkinson’s associated gene DJ-1 revealed in trophically impaired dopaminergic neurons. PLoS Biol 8(4):e1000349PubMedPubMedCentralCrossRefGoogle Scholar
  8. Asano T et al (2004) The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF-kappaB and c-Myc in pancreatic cancer cells. Oncogene 23(53):8571–8580PubMedCrossRefGoogle Scholar
  9. Avila J et al (2004) Role of tau protein in both physiological and pathological conditions. Physiol Rev 84(2):361–384PubMedCrossRefGoogle Scholar
  10. Billia F et al (2013) Parkinson-susceptibility gene DJ-1/PARK7 protects the murine heart from oxidative damage in vivo. Proc Natl Acad Sci U S A 110(15):6085–6090PubMedPubMedCentralCrossRefGoogle Scholar
  11. Blasi F, Carmeliet P (2002) uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol 3(12):932–943PubMedCrossRefGoogle Scholar
  12. Bonifati V et al (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299(5604):256–259PubMedCrossRefGoogle Scholar
  13. Bonifati V, Oostra BA, Heutink P (2004) Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson’s disease. J Mol Med (Berl) 82(3):163–174CrossRefGoogle Scholar
  14. Brognard J et al (2007) PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. Mol Cell 25(6):917–931PubMedCrossRefGoogle Scholar
  15. Burotto M et al (2014) The MAPK pathway across different malignancies: a new perspective. Cancer 120(22):3446–3456PubMedPubMedCentralCrossRefGoogle Scholar
  16. Canet-Aviles RM et al (2004) The Parkinson’s disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc Natl Acad Sci U S A 101(24):9103–9108PubMedPubMedCentralCrossRefGoogle Scholar
  17. Cao J et al (2014) The oxidation states of DJ-1 dictate the cell fate in response to oxidative stress triggered by 4-HPR: autophagy or apoptosis? Antioxid Redox Signal 21(10):1443–1459PubMedPubMedCentralCrossRefGoogle Scholar
  18. Cao J et al (2015) DJ-1 as a human oncogene and potential therapeutic target. Biochem Pharmacol 93(3):241–250PubMedCrossRefGoogle Scholar
  19. Cargnello M, Roux PP (2011) Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 75(1):50–83PubMedPubMedCentralCrossRefGoogle Scholar
  20. Caunt CJ et al (2015) MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road. Nat Rev Cancer 15(10):577–592PubMedCrossRefGoogle Scholar
  21. Chang HY et al (1998) Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx. Science 281(5384):1860–1863PubMedCrossRefGoogle Scholar
  22. Chang F et al (2003) Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia 17(7):1263–1293PubMedCrossRefGoogle Scholar
  23. Chen ZJ (2005) Ubiquitin signalling in the NF-kappaB pathway. Nat Cell Biol 7(8):758–765PubMedPubMedCentralCrossRefGoogle Scholar
  24. Chen ZJ, Sun LJ (2009) Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell 33(3):275–286PubMedCrossRefGoogle Scholar
  25. Choi MS et al (2014) Transnitrosylation from DJ-1 to PTEN attenuates neuronal cell death in parkinson’s disease models. J Neurosci 34(45):15123–15131PubMedPubMedCentralCrossRefGoogle Scholar
  26. Choi SK et al (2015) Overexpression of PI3K-p110alpha in the progression of uterine cervical neoplasia and its correlation with pAkt and DJ-1. Eur J Gynaecol Oncol 36(4):389–393PubMedGoogle Scholar
  27. Cross DA et al (1995) Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378(6559):785–789PubMedCrossRefGoogle Scholar
  28. Davidson B et al (2008) Expression and clinical role of DJ-1, a negative regulator of PTEN, in ovarian carcinoma. Hum Pathol 39(1):87–95PubMedCrossRefGoogle Scholar
  29. Devine MJ, Plun-Favreau H, Wood NW (2011) Parkinson’s disease and cancer: two wars, one front. Nat Rev Cancer 11(11):812–823PubMedCrossRefGoogle Scholar
  30. Dhillon AS et al (2002) Cyclic AMP-dependent kinase regulates Raf-1 kinase mainly by phosphorylation of serine 259. Mol Cell Biol 22(10):3237–3246PubMedPubMedCentralCrossRefGoogle Scholar
  31. Dongworth RK et al (2014) DJ-1 protects against cell death following acute cardiac ischemia-reperfusion injury. Cell Death Dis 5:e1082PubMedPubMedCentralCrossRefGoogle Scholar
  32. Eichhorn PJ et al (2007) A RNA interference screen identifies the protein phosphatase 2A subunit PR55gamma as a stress-sensitive inhibitor of c-SRC. PLoS Genet 3(12):e218PubMedPubMedCentralCrossRefGoogle Scholar
  33. Fan J et al (2008) DJ-1 decreases Bax expression through repressing p53 transcriptional activity. J Biol Chem 283(7):4022–4030PubMedCrossRefGoogle Scholar
  34. Fang M et al (2010) Role of DJ-1-induced PTEN down-regulation in migration and invasion of human glioma cells. Chin J Cancer 29(12):988–994PubMedCrossRefGoogle Scholar
  35. Feilotter HE et al (1999) Analysis of the 10q23 chromosomal region and the PTEN gene in human sporadic breast carcinoma. Br J Cancer 79(5–6):718–723PubMedPubMedCentralCrossRefGoogle Scholar
  36. Feng Z (2010) p53 Regulation of the IGF-1/AKT/mTOR pathways and the endosomal compartment. Cold Spring Harb Perspect Biol 2(2):a001057PubMedPubMedCentralCrossRefGoogle Scholar
  37. Franke TF et al (1997) Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate. Science 275(5300):665–668PubMedCrossRefGoogle Scholar
  38. Freihoff D et al (1999) Exclusion of a major role for the PTEN tumour-suppressor gene in breast carcinomas. Br J Cancer 79(5–6):754–758PubMedPubMedCentralCrossRefGoogle Scholar
  39. Fujino G et al (2007) Thioredoxin and TRAF family proteins regulate reactive oxygen species-dependent activation of ASK1 through reciprocal modulation of the N-terminal homophilic interaction of ASK1. Mol Cell Biol 27(23):8152–8163PubMedPubMedCentralCrossRefGoogle Scholar
  40. Gao T, Furnari F, Newton AC (2005) PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. Mol Cell 18(1):13–24PubMedCrossRefGoogle Scholar
  41. Gao H et al (2012) DJ-1 protects dopaminergic neurons against rotenone-induced apoptosis by enhancing ERK-dependent mitophagy. J Mol Biol 423(2):232–248PubMedCrossRefGoogle Scholar
  42. Geetha T, Jiang J, Wooten MW (2005) Lysine 63 polyubiquitination of the nerve growth factor receptor TrkA directs internalization and signaling. Mol Cell 20(2):301–312PubMedCrossRefGoogle Scholar
  43. Goldman EH, Chen L, Fu H (2004) Activation of apoptosis signal-regulating kinase 1 by reactive oxygen species through dephosphorylation at serine 967 and 14-3-3 dissociation. J Biol Chem 279(11):10442–10449PubMedCrossRefGoogle Scholar
  44. Green DR, Llambi F (2015) Cell death signaling. Cold Spring Harb Perspect Biol 7(12):a006080PubMedCrossRefGoogle Scholar
  45. Greer EL, Brunet A (2005) FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 24(50):7410–7425PubMedCrossRefGoogle Scholar
  46. Gu L et al (2009) Involvement of ERK1/2 signaling pathway in DJ-1-induced neuroprotection against oxidative stress. Biochem Biophys Res Commun 383(4):469–474PubMedCrossRefGoogle Scholar
  47. He X et al (2012) DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/uPA. Carcinogenesis 33(3):555–562PubMedCrossRefGoogle Scholar
  48. Hermanson E et al (2003) Nurr1 regulates dopamine synthesis and storage in MN9D dopamine cells. Exp Cell Res 288(2):324–334PubMedCrossRefGoogle Scholar
  49. Hwang S et al (2013) Drosophila DJ-1 decreases neural sensitivity to stress by negatively regulating Daxx-like protein through dFOXO. PLoS Genet 9(4):e1003412PubMedPubMedCentralCrossRefGoogle Scholar
  50. Ichijo H et al (1997) Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science 275(5296):90–94PubMedCrossRefGoogle Scholar
  51. Im JY et al (2010) DJ-1 protects against oxidative damage by regulating the thioredoxin/ASK1 complex. Neurosci Res 67(3):203–208PubMedPubMedCentralCrossRefGoogle Scholar
  52. Im JY et al (2012) DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway. Hum Mol Genet 21(13):3013–3024PubMedPubMedCentralCrossRefGoogle Scholar
  53. Ishikawa S et al (2009) Oxidative status of DJ-1-dependent activation of dopamine synthesis through interaction of tyrosine hydroxylase and 4-dihydroxy-L-phenylalanine (L-DOPA) decarboxylase with DJ-1. J Biol Chem 284(42):28832–28844PubMedPubMedCentralCrossRefGoogle Scholar
  54. Iwawaki T, Kohno K, Kobayashi K (2000) Identification of a potential nurr1 response element that activates the tyrosine hydroxylase gene promoter in cultured cells. Biochem Biophys Res Commun 274(3):590–595PubMedCrossRefGoogle Scholar
  55. James SR et al (1996) Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3,4,5-trisphosphate without subsequent activation. Biochem J 315(3):709–713PubMedPubMedCentralCrossRefGoogle Scholar
  56. Janssens V, Goris J (2001) Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J 353(3):417–439PubMedPubMedCentralCrossRefGoogle Scholar
  57. Jaramillo-Gomez J et al (2015) Overexpression of DJ-1 protects against C2-ceramide-induced neuronal death through activation of the PI3K/AKT pathway and inhibition of autophagy. Neurosci Lett 603:71–76PubMedCrossRefGoogle Scholar
  58. Jeffrey KL et al (2007) Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nat Rev Drug Discov 6(5):391–403PubMedCrossRefGoogle Scholar
  59. Junn E et al (2005) Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death. Proc Natl Acad Sci U S A 102(27):9691–9696PubMedPubMedCentralCrossRefGoogle Scholar
  60. Junttila MR, Li SP, Westermarck J (2008) Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival. FASEB J 22(4):954–965PubMedCrossRefGoogle Scholar
  61. Kahle PJ, Waak J, Gasser T (2009) DJ-1 and prevention of oxidative stress in Parkinson’s disease and other age-related disorders. Free Radic Biol Med 47(10):1354–1361PubMedCrossRefGoogle Scholar
  62. Karunakaran S et al (2007) Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death-associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson’s disease: protection by alpha-lipoic acid. FASEB J 21(9):2226–2236PubMedCrossRefGoogle Scholar
  63. Kato I et al (2013) Oxidized DJ-1 inhibits p53 by sequestering p53 from promoters in a DNA-binding affinity-dependent manner. Mol Cell Biol 33(2):340–359PubMedPubMedCentralCrossRefGoogle Scholar
  64. Keshet Y, Seger R (2010) The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions. Methods Mol Biol 661:3–38PubMedCrossRefGoogle Scholar
  65. Kim NW et al (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266(5193):2011–2015PubMedCrossRefGoogle Scholar
  66. Kim RH et al (2005) DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell 7(3):263–273PubMedCrossRefGoogle Scholar
  67. Kim YC et al (2009) Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN. Int J Oncol 35(6):1331–1341PubMedCrossRefGoogle Scholar
  68. Klawitter J et al (2013) Association of DJ-1/PTEN/AKT- and ASK1/p38-mediated cell signalling with ischaemic cardiomyopathy. Cardiovasc Res 97(1):66–76PubMedCrossRefGoogle Scholar
  69. Ko YG et al (2001) Apoptosis signal-regulating kinase 1 controls the proapoptotic function of death-associated protein (Daxx) in the cytoplasm. J Biol Chem 276(42):39103–39106PubMedCrossRefGoogle Scholar
  70. Kornberg MD et al (2010) GAPDH mediates nitrosylation of nuclear proteins. Nat Cell Biol 12(11):1094–1100PubMedPubMedCentralCrossRefGoogle Scholar
  71. Kramer ER et al (2007) Absence of ret signaling in mice causes progressive and late degeneration of the nigrostriatal system. PLoS Biol 5(3):e39PubMedPubMedCentralCrossRefGoogle Scholar
  72. Krebiehl G et al (2010) Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson’s disease-associated protein DJ-1. PLoS One 5(2):e9367PubMedPubMedCentralCrossRefGoogle Scholar
  73. Kruiswijk F, Labuschagne CF, Vousden KH (2015) p53 In survival, death and metabolic health: a lifeguard with a licence to kill. Nat Rev Mol Cell Biol 16(7):393–405PubMedCrossRefGoogle Scholar
  74. Laderoute KR et al (2006) 5′-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments. Mol Cell Biol 26(14):5336–5347PubMedPubMedCentralCrossRefGoogle Scholar
  75. Lawler S et al (1998) Synergistic activation of SAPK1/JNK1 by two MAP kinase kinases in vitro. Curr Biol 8(25):1387–1391PubMedCrossRefGoogle Scholar
  76. Lee KW et al (2012) Apoptosis signal-regulating kinase 1 mediates MPTP toxicity and regulates glial activation. PLoS One 7(1):e29935PubMedPubMedCentralCrossRefGoogle Scholar
  77. Leisner TM et al (2016) CIB1: a small protein with big ambitions. FASEB J 30(8):2640–2650PubMedPubMedCentralCrossRefGoogle Scholar
  78. Letourneux C, Rocher G, Porteu F (2006) B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK. EMBO J 25(4):727–738PubMedPubMedCentralCrossRefGoogle Scholar
  79. Lev N et al (2008) Oxidative insults induce DJ-1 upregulation and redistribution: implications for neuroprotection. Neurotoxicology 29(3):397–405PubMedCrossRefGoogle Scholar
  80. Lev N et al (2009) DJ-1 protects against dopamine toxicity. J Neural Transm (Vienna) 116(2):151–160CrossRefGoogle Scholar
  81. Lin E et al (2008) Rapid activation of ERK by 6-hydroxydopamine promotes survival of dopaminergic cells. J Neurosci Res 86(1):108–117PubMedCrossRefGoogle Scholar
  82. Lin J et al (2014) DJ-1 is activated in medulloblastoma and is associated with cell proliferation and differentiation. World J Surg Oncol 12:373PubMedPubMedCentralCrossRefGoogle Scholar
  83. Liu S et al (2015) DJ-1 knockdown inhibits growth and xenograft induced tumor generation of human hepatocellular carcinoma cells. Oncol Rep 33(1):201–206PubMedCrossRefGoogle Scholar
  84. Lu L et al (2012) DJ-1 upregulates tyrosine hydroxylase gene expression by activating its transcriptional factor Nurr1 via the ERK1/2 pathway. Int J Biochem Cell Biol 44(1):65–71PubMedCrossRefGoogle Scholar
  85. Lu L et al (2016) DJ-1/PARK7, but not its L166P mutant linked to autosomal recessive parkinsonism, modulates the transcriptional activity of the orphan nuclear receptor Nurr1 In vitro and in vivo. Mol Neurobiol 53:7363PubMedCrossRefGoogle Scholar
  86. Maehama T, Dixon JE (1998) The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273(22):13375–13378PubMedCrossRefGoogle Scholar
  87. Malgieri G, Eliezer D (2008) Structural effects of Parkinson’s disease linked DJ-1 mutations. Protein Sci 17(5):855–868PubMedPubMedCentralCrossRefGoogle Scholar
  88. Manning BD, Cantley LC (2007) AKT/PKB signaling: navigating downstream. Cell 129(7):1261–1274PubMedPubMedCentralCrossRefGoogle Scholar
  89. Martinat C et al (2004) Sensitivity to oxidative stress in DJ-1-deficient dopamine neurons: an ES- derived cell model of primary parkinsonism. PLoS Biol 2(11):e327PubMedPubMedCentralCrossRefGoogle Scholar
  90. Mathew R et al (2009) Autophagy suppresses tumorigenesis through elimination of p62. Cell 137(6):1062–1075PubMedPubMedCentralCrossRefGoogle Scholar
  91. Matsuzawa A et al (2005) ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity. Nat Immunol 6(6):587–592PubMedCrossRefGoogle Scholar
  92. Mayo LD, Donner DB (2002) The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network. Trends Biochem Sci 27(9):462–467PubMedCrossRefGoogle Scholar
  93. McCoy MK, Cookson MR (2014) DJ-1 regulation of mitochondrial function and autophagy through oxidative stress. Autophagy 7(5):531–532CrossRefGoogle Scholar
  94. McCubrey JA et al (2007) Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 1773(8):1263–1284PubMedCrossRefGoogle Scholar
  95. Menendez D, Inga A, Resnick MA (2009) The expanding universe of p53 targets. Nat Rev Cancer 9(10):724–737PubMedCrossRefGoogle Scholar
  96. Menzies FM, Yenisetti SC, Min KT (2005) Roles of drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress. Curr Biol 15(17):1578–1582PubMedCrossRefGoogle Scholar
  97. Meuillet EJ et al (2004) Thioredoxin-1 binds to the C2 domain of PTEN inhibiting PTEN’s lipid phosphatase activity and membrane binding: a mechanism for the functional loss of PTEN’s tumor suppressor activity. Arch Biochem Biophys 429(2):123–133PubMedCrossRefGoogle Scholar
  98. Meulener M et al (2005) Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson’s disease. Curr Biol 15(17):1572–1577PubMedCrossRefGoogle Scholar
  99. Milkovic NM et al (2015) Transient sampling of aggregation-prone conformations causes pathogenic instability of a parkinsonian mutant of DJ-1 at physiological temperature. Protein Sci 24(10):1671–1685PubMedPubMedCentralCrossRefGoogle Scholar
  100. Mo JS et al (2008) DJ-1 modulates UV-induced oxidative stress signaling through the suppression of MEKK1 and cell death. Cell Death Differ 15(6):1030–1041PubMedCrossRefGoogle Scholar
  101. Mo JS et al (2010) DJ-1 modulates the p38 mitogen-activated protein kinase pathway through physical interaction with apoptosis signal-regulating kinase 1. J Cell Biochem 110(1):229–237PubMedGoogle Scholar
  102. Moore DJ et al (2003) A missense mutation (L166P) in DJ-1, linked to familial Parkinson’s disease, confers reduced protein stability and impairs homo-oligomerization. J Neurochem 87(6):1558–1567PubMedCrossRefGoogle Scholar
  103. Moscat J, Diaz-Meco MT (2009) p62 at the crossroads of autophagy, apoptosis, and cancer. Cell 137(6):1001–1004PubMedPubMedCentralCrossRefGoogle Scholar
  104. Mukherjee UA et al (2011) 37 A novel role for DJ-1 in cardioprotection. Heart 97(24):e8CrossRefGoogle Scholar
  105. Mut M et al (2012) Both mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinases (ERK) 1/2 and phosphatidylinositide-3-OH kinase (PI3K)/Akt pathways regulate activation of E-twenty-six (ETS)-like transcription factor 1 (Elk-1) in U138 glioblastoma cells. Int J Biochem Cell Biol 44(2):302–310PubMedCrossRefGoogle Scholar
  106. Nagakubo D et al (1997) DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras. Biochem Biophys Res Commun 231(2):509–513PubMedCrossRefGoogle Scholar
  107. Nakamura T, Lipton SA (2013) Emerging role of protein-protein transnitrosylation in cell signaling pathways. Antioxid Redox Signal 18(3):239–249PubMedPubMedCentralCrossRefGoogle Scholar
  108. New L, Jiang Y, Han J (2003) Regulation of PRAK subcellular location by p38 MAP kinases. Mol Biol Cell 14(6):2603–2616PubMedPubMedCentralCrossRefGoogle Scholar
  109. Niki T et al (2003) DJBP: a novel DJ-1-binding protein, negatively regulates the androgen receptor by recruiting histone deacetylase complex, and DJ-1 antagonizes this inhibition by abrogation of this complex. Mol Cancer Res 1(4):247–261PubMedGoogle Scholar
  110. Nishitoh H et al (1998) ASK1 is essential for JNK/SAPK activation by TRAF2. Mol Cell 2(3):389–395PubMedCrossRefGoogle Scholar
  111. Nordzell M et al (2004) Defining an N-terminal activation domain of the orphan nuclear receptor Nurr1. Biochem Biophys Res Commun 313(1):205–211PubMedCrossRefGoogle Scholar
  112. O’Hara L, Smith LB (2015) Androgen receptor roles in spermatogenesis and infertility. Best Pract Res Clin Endocrinol Metab 29(4):595–605PubMedCrossRefGoogle Scholar
  113. Oehrl W, Rubio I, Wetzker R (2003) Serine 338 phosphorylation is dispensable for activation of c-Raf1. J Biol Chem 278(20):17819–17826PubMedCrossRefGoogle Scholar
  114. Parsanejad M et al (2014) Regulation of the VHL/HIF-1 pathway by DJ-1. J Neurosci 34(23):8043–8050PubMedCrossRefGoogle Scholar
  115. Perren A et al (1999) Immunohistochemical evidence of loss of PTEN expression in primary ductal adenocarcinomas of the breast. Am J Pathol 155(4):1253–1260PubMedPubMedCentralCrossRefGoogle Scholar
  116. Pitkanen-Arsiola T et al (2006) Androgen and anti-androgen treatment modulates androgen receptor activity and DJ-1 stability. Prostate 66(11):1177–1193PubMedCrossRefGoogle Scholar
  117. Plotnikov A et al (2011) The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation. Biochim Biophys Acta 1813(9):1619–1633PubMedCrossRefGoogle Scholar
  118. Pype S et al (2000) TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that inhibits nuclear factor-kappa B activation. J Biol Chem 275(24):18586–18593PubMedCrossRefGoogle Scholar
  119. Rahman-Roblick R et al (2008) Proteomic identification of p53-dependent protein phosphorylation. Oncogene 27(35):4854–4859PubMedCrossRefGoogle Scholar
  120. Ravi R et al (2000) Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev 14(1):34–44PubMedPubMedCentralGoogle Scholar
  121. Ren H et al (2010) DJ-1, a cancer and Parkinson’s disease associated protein, regulates autophagy through JNK pathway in cancer cells. Cancer Lett 297(1):101–108PubMedCrossRefGoogle Scholar
  122. Repici M et al (2013) Parkinson’s Disease-associated mutations in DJ-1 modulate its dimerization in living cells. J Mol Med (Berl) 91(5):599–611CrossRefGoogle Scholar
  123. Ries V et al (2006) Oncoprotein Akt/PKB induces trophic effects in murine models of Parkinson’s disease. Proc Natl Acad Sci U S A 103(49):18757–18762PubMedPubMedCentralCrossRefGoogle Scholar
  124. Saitoh M et al (1998) Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J 17(9):2596–2606PubMedPubMedCentralCrossRefGoogle Scholar
  125. Sekito A et al (2006) DJ-1 interacts with HIPK1 and affects H2O2-induced cell death. Free Radic Res 40(2):155–165PubMedCrossRefGoogle Scholar
  126. Shamoto-Nagai M et al (2003) An inhibitor of mitochondrial complex I, rotenone, inactivates proteasome by oxidative modification and induces aggregation of oxidized proteins in SH-SY5Y cells. J Neurosci Res 74(4):589–597PubMedCrossRefGoogle Scholar
  127. Shendelman S et al (2004) DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation. PLoS Biol 2(11):e362PubMedPubMedCentralCrossRefGoogle Scholar
  128. Shi W et al (2003) Dysregulated PTEN-PKB and negative receptor status in human breast cancer. Int J Cancer 104(2):195–203PubMedCrossRefGoogle Scholar
  129. Shih HM et al (2007) Daxx mediates SUMO-dependent transcriptional control and subnuclear compartmentalization. Biochem Soc Trans 35(Pt 6):1397–1400PubMedCrossRefGoogle Scholar
  130. Shinbo Y et al (2005) Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities. Cell Death Differ 13(1):96–108CrossRefGoogle Scholar
  131. Silverstein AM et al (2002) Actions of PP2A on the MAP kinase pathway and apoptosis are mediated by distinct regulatory subunits. Proc Natl Acad Sci 99(7):4221–4226PubMedPubMedCentralCrossRefGoogle Scholar
  132. Sitaram RT et al (2009) The PTEN regulator DJ-1 is associated with hTERT expression in clear cell renal cell carcinoma. Int J Cancer 125(4):783–790PubMedCrossRefGoogle Scholar
  133. Sonoda Y et al (1997) Stimulation of Interleukin-8 production by Okadaic acid and vanadate in a human Promyelocyte cell line, an HL-60 subline: possible role of mitogen-activated protein kinase on the Okadaic acid-induced nf-κb activation. J Biol Chem 272(24):15366–15372PubMedCrossRefGoogle Scholar
  134. Sorescu D et al (2002) Superoxide production and expression of Nox family proteins in human atherosclerosis. Circulation 105(12):1429PubMedCrossRefGoogle Scholar
  135. Taira T et al (2004a) DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep 5(2):213–218PubMedPubMedCentralCrossRefGoogle Scholar
  136. Taira T, Iguchi-Ariga SM, Ariga H (2004b) Co-localization with DJ-1 is essential for the androgen receptor to exert its transcription activity that has been impaired by androgen antagonists. Biol Pharm Bull 27(4):574–577PubMedCrossRefGoogle Scholar
  137. Takahashi K et al (2001) DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor. J Biol Chem 276(40):37556–37563PubMedCrossRefGoogle Scholar
  138. Takahashi-Niki K et al (2004) Reduced anti-oxidative stress activities of DJ-1 mutants found in Parkinson’s disease patients. Biochem Biophys Res Commun 320(2):389–397PubMedCrossRefGoogle Scholar
  139. Takahashi-Niki K et al (2015) Epidermal growth factor-dependent activation of the extracellular signal-regulated kinase pathway by DJ-1 protein through its direct binding to c-Raf protein. J Biol Chem 290(29):17838–17847PubMedPubMedCentralCrossRefGoogle Scholar
  140. Takakura M et al (1999) Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. Cancer Res 59(3):551–557PubMedGoogle Scholar
  141. Tang J et al (2014) PRAK interacts with DJ-1 and prevents oxidative stress-induced cell death. Oxidative Med Cell Longev 2014:735618Google Scholar
  142. Tentolouris C et al (2004) Endothelial function and proinflammatory cytokines in patients with ischemic heart disease and dilated cardiomyopathy. Int J Cardiol 94(2):301–305PubMedCrossRefGoogle Scholar
  143. Tillman JE et al (2007) DJ-1 binds androgen receptor directly and mediates its activity in hormonally treated prostate cancer cells. Cancer Res 67(10):4630–4637PubMedCrossRefGoogle Scholar
  144. Tobiume K et al (2001) ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep 2(3):222–228PubMedPubMedCentralCrossRefGoogle Scholar
  145. van der Brug MP et al (2008) RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways. Proc Natl Acad Sci U S A 105(29):10244–10249PubMedPubMedCentralCrossRefGoogle Scholar
  146. Varady G, Sarkadi B, Fatyol K (2011) TTRAP is a novel component of the non-canonical TRAF6-TAK1 TGF-beta signaling pathway. PLoS One 6(9):e25548PubMedPubMedCentralCrossRefGoogle Scholar
  147. Vasseur S et al (2009) DJ-1/PARK7 is an important mediator of hypoxia-induced cellular responses. Proc Natl Acad Sci U S A 106(4):1111–1116PubMedPubMedCentralCrossRefGoogle Scholar
  148. Vasseur S et al (2012) Consequences of DJ-1 upregulation following p53 loss and cell transformation. Oncogene 31(5):664–670PubMedGoogle Scholar
  149. Vilotti S et al (2012) Parkinson’s disease DJ-1 L166P alters rRNA biogenesis by exclusion of TTRAP from the nucleolus and sequestration into cytoplasmic aggregates via TRAF6. PLoS One 7(4):e35051PubMedPubMedCentralCrossRefGoogle Scholar
  150. Vousden KH, Prives C (2009) Blinded by the light: the growing complexity of p53. Cell 137(3):413–431PubMedCrossRefGoogle Scholar
  151. Waak J et al (2009) Oxidizable residues mediating protein stability and cytoprotective interaction of DJ-1 with apoptosis signal-regulating kinase 1. J Biol Chem 284(21):14245–14257PubMedPubMedCentralCrossRefGoogle Scholar
  152. Wang J et al (2009) A non-canonical MEK/ERK signaling pathway regulates autophagy via regulating Beclin 1. J Biol Chem 284(32):21412–21424PubMedPubMedCentralCrossRefGoogle Scholar
  153. Wang Z et al (2011) DJ-1 modulates the expression of cu/Zn-superoxide dismutase-1 through the Erk1/2-Elk1 pathway in neuroprotection. Ann Neurol 70(4):591–599PubMedCrossRefGoogle Scholar
  154. Wang Y et al (2013) Parkinson’s Disease-associated DJ-1 mutations increase abnormal phosphorylation of tau protein through Akt/GSK-3beta pathways. J Mol Neurosci 51(3):911–918PubMedCrossRefGoogle Scholar
  155. West AB, Dawson VL, Dawson TM (2005) To die or grow: Parkinson’s disease and cancer. Trends Neurosci 28(7):348–352PubMedCrossRefGoogle Scholar
  156. Whitmarsh AJ, Davis RJ (1998) Structural organization of MAP-kinase signaling modules by scaffold proteins in yeast and mammals. Trends Biochem Sci 23(12):481–485PubMedCrossRefGoogle Scholar
  157. Wilson MA (2011) The role of cysteine oxidation in DJ-1 function and dysfunction. Antioxid Redox Signal 15(1):111–122PubMedPubMedCentralCrossRefGoogle Scholar
  158. Wu KJ et al (1999) Direct activation of TERT transcription by c-MYC. Nat Genet 21(2):220–224PubMedCrossRefGoogle Scholar
  159. Xu L, Glass CK, Rosenfeld MG (1999) Coactivator and corepressor complexes in nuclear receptor function. Curr Opin Genet Dev 9(2):140–147PubMedCrossRefGoogle Scholar
  160. Xu P et al (2009) Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 137(1):133–145PubMedPubMedCentralCrossRefGoogle Scholar
  161. Yang Y et al (2005) Inactivation of drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signaling. Proc Natl Acad Sci U S A 102(38):13670–13675PubMedPubMedCentralCrossRefGoogle Scholar
  162. Yao Y et al (2011) Upregulated DJ-1 promotes renal tubular EMT by suppressing cytoplasmic PTEN expression and Akt activation. J Huazhong Univ Sci Technolog Med Sci 31(4):469–475PubMedCrossRefGoogle Scholar
  163. Yoon KW et al (2009) CIB1 Functions as a ca(2+)-sensitive modulator of stress-induced signaling by targeting ASK1. Proc Natl Acad Sci U S A 106(41):17389–17394PubMedPubMedCentralCrossRefGoogle Scholar
  164. Yoshioka K (2004) Scaffold proteins in mammalian MAP kinase cascades. J Biochem 135(6):657–661PubMedCrossRefGoogle Scholar
  165. Zanassi P et al (2001) cAMP-dependent protein kinase induces cAMP-response element-binding protein phosphorylation via an intracellular calcium release/ERK-dependent pathway in striatal neurons. J Biol Chem 276(15):11487–11495PubMedCrossRefGoogle Scholar
  166. Zhan H et al (2010) Ataxia telangiectasia mutated (ATM)-mediated DNA damage response in oxidative stress-induced vascular endothelial cell senescence. J Biol Chem 285(38):29662–29670PubMedPubMedCentralCrossRefGoogle Scholar
  167. Zhang X et al (2011) Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta (BBA) Mol Cell Res 1813(11):1978–1986CrossRefGoogle Scholar
  168. Zhang Y et al (2016) Protective effects of DJ-1 medicated Akt phosphorylation on mitochondrial function are promoted by da-Bu-yin-wan in 1-methyl-4-phenylpyridinium-treated human neuroblastoma SH-SY5Y cells. J Ethnopharmacol 187:83–93PubMedCrossRefGoogle Scholar
  169. Zhong H et al (2000) Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res 60(6):1541–1545PubMedGoogle Scholar
  170. Zhou B et al (2002) The specificity of extracellular signal-regulated kinase 2 dephosphorylation by protein phosphatases. J Biol Chem 277(35):31818–31825PubMedCrossRefGoogle Scholar
  171. Zhou J et al (2015) Crosstalk between MAPK/ERK and PI3K/AKT signal pathways during brain ischemia/reperfusion. ASN Neuro 7(5):175909141560246CrossRefGoogle Scholar
  172. Zhu ZM et al (2014) DJ-1 is involved in the peritoneal metastasis of gastric cancer through activation of the Akt signaling pathway. Oncol Rep 31(3):1489–1497PubMedCrossRefGoogle Scholar
  173. Zucchelli S et al (2009) Aggresome-forming TTRAP mediates pro-apoptotic properties of Parkinson’s disease-associated DJ-1 missense mutations. Cell Death Differ 16(3):428–438PubMedCrossRefGoogle Scholar
  174. Zucchelli S et al (2010) TRAF6 promotes atypical ubiquitination of mutant DJ-1 and alpha-synuclein and is localized to Lewy bodies in sporadic Parkinson’s disease brains. Hum Mol Genet 19(19):3759–3770PubMedCrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Center for Neurodegenerative and Neuroimmunologic Diseases, Department of NeurologyRutgers – Robert Wood Johnson Medical SchoolPiscatawayUSA

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