Skip to main content

Advertisement

Log in

Characterizing the novel protein p33MONOX

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The novel protein p33MONOX (p33Monooxygenase) was over-expressed in neuroblastoma cells demonstrating its inhibitory effect on the phosphorylation of the App (amyloid precursor protein) and Bcl2 (B-cell lymphoma 2) proteins but mediating higher activation of Mapk1/3 (mitogen-activated protein kinase 1/3). We employed a variety of cell biology techniques to show the localization of p33MONOX to the cytoplasm of pyramidal neurons in the mouse brain hippocampus. We also carried out a yeast-two-hybrid screening plus co-immunoprecipitation and bio-informatics to determine COBRA1 (cofactor of BRCA1 (breast cancer type 1)), NOL12 (nucleolar protein 12), and PRNP (prion protein) as p33MONOX-interacting proteins. Bio-computational analyses revealed a flavine-containing monooxygenase (FMO)-1 motif, thus linking p33MONOX to a group of previously characterized proteins, the MICALs (molecule interacting with CasL). Concluding, p33MONOX might regulate pre- and post-transcriptional control of dynamic processes related to growth cone guidance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Welsh KA, Butters N, Hughes JP, Mohs RC, Heyman A (1992) Detection and staging of dementia in Alzheimer’s disease. Use of the neuropsychological measures developed for the Consortium to Establish a Registry for Alzheimer’s Disease. Arch Neurol 49:448–452

    PubMed  CAS  Google Scholar 

  2. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30:572–580

    Article  PubMed  CAS  Google Scholar 

  3. Heese K, Akatsu H (2006) Alzheimer’s disease—an interactive perspective. Curr Alzheimer Res 3:109–121

    Article  PubMed  CAS  Google Scholar 

  4. Mattson MP (2004) Pathways towards and away from Alzheimer’s disease. Nature 430:631–639

    Article  PubMed  CAS  Google Scholar 

  5. Selkoe DJ, Schenk D (2003) Alzheimer’s disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 43:545–584

    Article  PubMed  CAS  Google Scholar 

  6. Butterfield DA (2002) Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer’s disease brain. A review. Free Radic Res 36:1307–1313

    Article  PubMed  CAS  Google Scholar 

  7. Butterfield DA, Castegna A, Lauderback CM, Drake J (2002) Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer’s disease brain contribute to neuronal death. Neurobiol Aging 23:655–664

    Article  PubMed  Google Scholar 

  8. Pappolla MA, Chyan YJ, Omar RA, Hsiao K, Perry G, Smith MA, Bozner P (1998) Evidence of oxidative stress and in vivo neurotoxicity of beta-amyloid in a transgenic mouse model of Alzheimer’s disease: a chronic oxidative paradigm for testing antioxidant therapies in vivo. Am J Pathol 152:871–877

    PubMed  CAS  Google Scholar 

  9. Yokota T, Mishra M, Akatsu H, Tani Y, Miyauchi T, Yamamoto T, Kosaka K, Nagai Y, Sawada T, Heese K (2006) Brain site-specific gene expression analysis in Alzheimer’s disease patients. Eur J Clin Invest 36:820–830

    Article  PubMed  CAS  Google Scholar 

  10. Heese K, Yamada T, Akatsu H, Yamamoto T, Kosaka K, Nagai Y, Sawada T (2004) Characterizing the new transcription regulator protein p60TRP. J Cell Biochem 91:1030–1042

    Article  PubMed  CAS  Google Scholar 

  11. Nehar S, Mishra M, Heese K (2009) Identification and characterisation of the novel amyloid-beta peptide-induced protein p17. FEBS Lett 583:3247–3253

    Article  PubMed  CAS  Google Scholar 

  12. Massey V (1995) Introduction: flavoprotein structure and mechanism. FASEB J 9:473–475

    PubMed  CAS  Google Scholar 

  13. Yeung CK, Lang DH, Thummel KE, Rettie AE (2000) Immunoquantitation of FMO1 in human liver, kidney, and intestine. Drug Metab Dispos 28:1107–1111

    PubMed  CAS  Google Scholar 

  14. Ziegler DM (1990) Flavin-containing monooxygenases: enzymes adapted for multisubstrate specificity. Trends Pharmacol Sci 11:321–324

    Article  PubMed  CAS  Google Scholar 

  15. Massey V (1994) Activation of molecular oxygen by flavins and flavoproteins. J Biol Chem 269:22459–22462

    PubMed  CAS  Google Scholar 

  16. Lee MS, Kao SC, Lemere CA, Xia W, Tseng HC, Zhou Y, Neve R, Ahlijanian MK, Tsai LH (2003) APP processing is regulated by cytoplasmic phosphorylation. J Cell Biol 163:83–95

    Article  PubMed  CAS  Google Scholar 

  17. Ito T, Deng X, Carr B, May WS (1997) Bcl-2 phosphorylation required for anti-apoptosis function. J Biol Chem 272:11671–11673

    Article  PubMed  CAS  Google Scholar 

  18. Deng X, Ito T, Carr B, Mumby M, May WS Jr (1998) Reversible phosphorylation of Bcl2 following interleukin 3 or bryostatin 1 is mediated by direct interaction with protein phosphatase 2A. J Biol Chem 273:34157–34163

    Article  PubMed  CAS  Google Scholar 

  19. Deng X, Gao F, Flagg T, May WS Jr (2004) Mono- and multisite phosphorylation enhances Bcl2’s antiapoptotic function and inhibition of cell cycle entry functions. Proc Natl Acad Sci USA 101:153–158

    Article  PubMed  CAS  Google Scholar 

  20. Yamamoto K, Ichijo H, Korsmeyer SJ (1999) BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol 19:8469–8478

    PubMed  CAS  Google Scholar 

  21. Chang BS, Minn AJ, Muchmore SW, Fesik SW, Thompson CB (1997) Identification of a novel regulatory domain in Bcl-X(L) and Bcl-2. EMBO J 16:968–977

    Article  PubMed  CAS  Google Scholar 

  22. Liu XA, Liao K, Liu R, Wang HH, Zhang Y, Zhang Q, Wang Q, Li HL, Tian Q, Wang JZ (2010) Tau dephosphorylation potentiates apoptosis by mechanisms involving a failed dephosphorylation/activation of Bcl-2. J Alzheimer’s Dis 19:953–962

    CAS  Google Scholar 

  23. Kholodenko BN (2007) Untangling the signalling wires. Nat Cell Biol 9:247–249

    Article  PubMed  CAS  Google Scholar 

  24. McChesney PA, Aiyar SE, Lee OJ, Zaika A, Moskaluk C, Li R, El-Rifai W (2006) Cofactor of BRCA1: a novel transcription factor regulator in upper gastrointestinal adenocarcinomas. Cancer Res 66:1346–1353

    Article  PubMed  CAS  Google Scholar 

  25. Kramer PR, Wray S (2001) Nasal embryonic LHRH factor (NELF) expression within the CNS and PNS of the rodent. Brain Res Gene Expr Patterns 1:23–26

    Article  PubMed  CAS  Google Scholar 

  26. Kramer PR, Wray S (2000) Novel gene expressed in nasal region influences outgrowth of olfactory axons and migration of luteinizing hormone-releasing hormone (LHRH) neurons. Genes Dev 14:1824–1834

    PubMed  CAS  Google Scholar 

  27. Sun J, Blair AL, Aiyar SE, Li R (2007) Cofactor of BRCA1 modulates androgen-dependent transcription and alternative splicing. J Steroid Biochem Mol Biol 107:131–139

    Article  PubMed  CAS  Google Scholar 

  28. Narita T, Yamaguchi Y, Yano K, Sugimoto S, Chanarat S, Wada T, Kim DK, Hasegawa J, Omori M, Inukai N, Endoh M, Yamada T, Handa H (2003) Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex. Mol Cell Biol 23:1863–1873

    Article  PubMed  CAS  Google Scholar 

  29. Suzuki S, Kanno M, Fujiwara T, Sugiyama H, Yokoyama A, Takahashi H, Tanaka J (2006) Molecular cloning and characterization of Nop25, a novel nucleolar RNA binding protein, highly conserved in vertebrate species. Exp Cell Res 312:1031–1041

    Article  PubMed  CAS  Google Scholar 

  30. Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksoz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (2005) A human protein–protein interaction network: a resource for annotating the proteome. Cell 122:957–968

    Article  PubMed  CAS  Google Scholar 

  31. Juanes ME, Elvira G, Garcia-Grande A, Calero M, Gasset M (2009) Biosynthesis of prion protein nucleocytoplasmic isoforms by alternative initiation of translation. J Biol Chem 284:2787–2794

    Article  PubMed  CAS  Google Scholar 

  32. Satoh J, Obayashi S, Misawa T, Sumiyoshi K, Oosumi K, Tabunoki H (2009) Protein microarray analysis identifies human cellular prion protein interactors. Neuropathol Appl Neurobiol 35:16–35

    Article  PubMed  CAS  Google Scholar 

  33. Haigh CL, Lewis VA, Vella LJ, Masters CL, Hill AF, Lawson VA, Collins SJ (2009) PrPC-related signal transduction is influenced by copper, membrane integrity and the alpha cleavage site. Cell Res 19:1062–1078

    Article  PubMed  CAS  Google Scholar 

  34. Haitina T, Lindblom J, Renstrom T, Fredriksson R (2006) Fourteen novel human members of mitochondrial solute carrier family 25 (SLC25) widely expressed in the central nervous system. Genomics 88:779–790

    Article  PubMed  CAS  Google Scholar 

  35. Miao L, St Clair DK (2009) Regulation of superoxide dismutase genes: implications in disease. Free Radic Biol Med 47:344–356

    Article  PubMed  CAS  Google Scholar 

  36. Lynn S, Huang EJ, Elchuri S, Naeemuddin M, Nishinaka Y, Yodoi J, Ferriero DM, Epstein CJ, Huang TT (2005) Selective neuronal vulnerability and inadequate stress response in superoxide dismutase mutant mice. Free Radic Biol Med 38:817–828

    Article  PubMed  CAS  Google Scholar 

  37. Terman JR, Mao T, Pasterkamp RJ, Yu HH, Kolodkin AL (2002) MICALs, a family of conserved flavoprotein oxidoreductases, function in plexin-mediated axonal repulsion. Cell 109:887–900

    Article  PubMed  CAS  Google Scholar 

  38. Massey V, Palmer G (1966) On the existence of spectrally distinct classes of flavoprotein semiquinones. A new method for the quantitative production of flavoprotein semiquinones. Biochemistry 5:3181–3189

    Article  PubMed  CAS  Google Scholar 

  39. Ventura A, Pelicci PG (2002) Semaphorins: green light for redox signaling? Sci STKE 2002: pe44

  40. Kamata H, Hirata H (1999) Redox regulation of cellular signalling. Cell Signal 11:1–14

    Article  PubMed  CAS  Google Scholar 

  41. Finkel T (1998) Oxygen radicals and signaling. Curr Opin Cell Biol 10:248–253

    Article  PubMed  CAS  Google Scholar 

  42. Meng TC, Fukada T, Tonks NK (2002) Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol Cell 9:387–399

    Article  PubMed  CAS  Google Scholar 

  43. Juurlink BH, Paterson PG (1998) Review of oxidative stress in brain and spinal cord injury: suggestions for pharmacological and nutritional management strategies. J Spinal Cord Med 21:309–334

    PubMed  CAS  Google Scholar 

  44. Lovell MA, Ehmann WD, Butler SM, Markesbery WR (1995) Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer’s disease. Neurology 45:1594–1601

    Google Scholar 

  45. Schuessel K, Leutner S, Cairns NJ, Muller WE, Eckert A (2004) Impact of gender on upregulation of antioxidant defence mechanisms in Alzheimer’s disease brain. J Neural Transm 111:1167–1182

    Article  PubMed  CAS  Google Scholar 

  46. Nunomura A, Chiba S, Lippa CF, Cras P, Kalaria RN, Takeda A, Honda K, Smith MA, Perry G (2004) Neuronal RNA oxidation is a prominent feature of familial Alzheimer’s disease. Neurobiol Dis 17:108–113

    Article  PubMed  CAS  Google Scholar 

  47. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA (2001) Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci 21:3017–3023

    PubMed  CAS  Google Scholar 

  48. Behl C (2005) Oxidative stress in Alzheimer’s disease: implications for prevention and therapy. Subcell Biochem 38:65–78

    Article  PubMed  CAS  Google Scholar 

  49. Reddy PH (2006) Amyloid precursor protein-mediated free radicals and oxidative damage: implications for the development and progression of Alzheimer’s disease. J Neurochem 96:1–13

    Article  PubMed  CAS  Google Scholar 

  50. Premkumar DR, Smith MA, Richey PL, Petersen RB, Castellani R, Kutty RK, Wiggert B, Perry G, Kalaria RN (1995) Induction of heme oxygenase-1 mRNA and protein in neocortex and cerebral vessels in Alzheimer’s disease. J Neurochem 65:1399–1402

    Article  PubMed  CAS  Google Scholar 

  51. Schipper HM, Cisse S, Stopa EG (1995) Expression of heme oxygenase-1 in the senescent and Alzheimer-diseased brain. Ann Neurol 37:758–768

    Article  PubMed  CAS  Google Scholar 

  52. Smith MA, Kutty RK, Richey PL, Yan SD, Stern D, Chader GJ, Wiggert B, Petersen RB, Perry G (1994) Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer’s disease. Am J Pathol 145:42–47

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by an A*STAR grant (BMRC/04/1/22/19/360) to K.H. We thank Ms H.J. Tang and S. Yusof (both from the School of Biological Sciences, Nanyang Technical University) for technical assistance. We are particularly grateful to Prof. Dr. R. Li (Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center, 15355 Lambda Drive, San Antonio, TX, 78245-3207, USA) for providing us the anti-COBRA1 antibody.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Klaus Heese.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mishra, M., Inoue, N. & Heese, K. Characterizing the novel protein p33MONOX. Mol Cell Biochem 350, 127–134 (2011). https://doi.org/10.1007/s11010-010-0690-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-010-0690-4

Keywords

Navigation