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Activity-Dependent Neuroprotective Protein Modulates Its Own Gene Expression

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Abstract

We investigated whether activity-dependent neuroprotective protein (ADNP) could autoregulate its own expression. Both the endogenous ADNP gene and reporter gene constructs were analysed in response to overexpression of ADNP, supplied either as wild-type ADNP or a mutant form lacking the NAP motif, a motif which has neuroprotective properties. Overexpression of these two forms of ADNP resulted in both decreased endogenous ADNP expression and repressed ADNP promoter-directed reporter gene activity. Chromatin immunoprecipitation demonstrated the ability of ADNP to bind to its own promoter which is consistent with its action as a repressor of both promoter-supported and endogenous ADNP expression.

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Abbreviations

PCR:

Polymerase chain reaction

bp:

Base pair

m:

Minutes

s:

Seconds

References

  • Bassan M, Zamostiano R, Davidson A et al (1999) Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide. J Neurochem 72:1283–1293

    Article  PubMed  CAS  Google Scholar 

  • Becskei A, Serrano L (2000) Engineering stability in gene networks by autoregulation. Nature 405:590–593

    Article  PubMed  CAS  Google Scholar 

  • Benayoun BA, Batista F, Auer J, Dipietromaria A, L'Hote D, De Baere E, Veitia RA (2009) Positive and negative feedback regulates the transcription factor FOXL2 in response to cell stress: evidence for a regulatory imbalance induced by disease-causing mutations. Hum Mol Genet 18:632–644

    Article  PubMed  CAS  Google Scholar 

  • Brenneman DE, Spong CY, Gozes I (2000) Protective peptides derived from novel glial proteins. Biochem Soc Trans 28:452–455

    Article  PubMed  CAS  Google Scholar 

  • Cosgrave AS, McKay JS, Bubb V, Morris R, Quinn JP, Thippeswamy T (2008) Regulation of activity-dependent neuroprotective protein (ADNP) by the NO-cGMP pathway in the hippocampus during kainic acid-induced seizure. Neurobiol Dis 30:281–292

    Article  PubMed  CAS  Google Scholar 

  • Coulson JM, Fiskerstrand CE, Woll PJ, Quinn JP (1999) Arginine vasopressin promoter regulation is mediated by a neuron- restrictive silencer element in small cell lung cancer. Canc Res 59:5123–5127

    CAS  Google Scholar 

  • Dangoor D, Giladi E, Fridkin M, Gozes I (2005) Neuropeptide receptor transcripts are expressed in the rat clitoris and oscillate during the estrus cycle in the rat vagina. Peptides 26:2579–2584

    Article  PubMed  CAS  Google Scholar 

  • Divinski I, Holtser-Cochav M, Vulih-Schultzman I, Steingart RA, Gozes I (2006) Peptide neuroprotection through specific interaction with brain tubulin. J Neurochem 98:973–984

    Article  PubMed  CAS  Google Scholar 

  • Dresner E, Agam G, Gozes I (2011) Activity-dependent neuroprotective protein (ADNP) expression level is correlated with the expression of the sister protein ADNP2: deregulation in schizophrenia. Eur Neuropsychopharmacol 21:355–361

    Article  PubMed  CAS  Google Scholar 

  • Furman S, Steingart RA, Mandel S, Hauser JM, Brenneman DE, Gozes I (2004) Subcellular localisation and secretion of activity-dependent neuroprotective protein in astrocytes. Neuron Glia Biol 1:193–199

    Article  PubMed  Google Scholar 

  • Furman S, Hill JM, Vulih I, Zaltzman R, Hauser JM, Brenneman DE, Gozes I (2005) Sexual dimorphism of activity-dependent neuroprotective protein in the mouse arcuate nucleus. Neurosci Lett 373:73–78

    Article  PubMed  CAS  Google Scholar 

  • Gennet N, Herden C, Bubb VJ, Quinn JP, Kipar A (2008) Expression of activity-dependent neuroprotective protein in the brain of adult rats. Histol Histopathol 23:309–317

    PubMed  CAS  Google Scholar 

  • Gozes I, Divinsky I, Pilzer I, Fridkin M, Brenneman DE, Spier AD (2003) From vasoactive intestinal peptide (VIP) through activity-dependent neuroprotective protein (ADNP) to NAP: a view of neuroprotection and cell division. J Mol Neurosci 20:315–322

    Article  PubMed  CAS  Google Scholar 

  • Leker RR, Teichner A, Grigoriadis N, Ovadia H, Brenneman DE, Fridkin M, Giladi E, Romano J, Gozes I (2002) NAP, a femtomolar-acting peptide, protects the brain against ischemic injury by reducing apoptotic death. Stroke 33:1085–1092

    Article  PubMed  CAS  Google Scholar 

  • Mandel S, Gozes I (2007) Activity-dependent neuroprotective protein constitutes a novel element in the SWI/SNF chromatin remodeling complex. J Biol Chem 282:34448–34456

    Article  PubMed  CAS  Google Scholar 

  • Mandel S, Spivak-Pohis I, Gozes I (2008) ADNP differential nucleus/cytoplasm localization in neurons suggests multiple roles in neuronal differentiation and maintenance. J Mol Neurosci 35:127–141

    Article  PubMed  CAS  Google Scholar 

  • Mendelson SC, Morrison CF, McAllister J, Paterson JM, Dobson SP, Mulderry PK, Quinn JP (1995) Repression of preprotachykinin-A promoter activity is mediated by proximal promoter element. Neuroscience 65:837–847

    Article  PubMed  CAS  Google Scholar 

  • Pinhasov A, Mandel S, Torchinsky A, Giladi E, Pittel Z, Goldsweig AM, Servoss SJ, Brenneman DE, Gozes I (2003) Activity-dependent neuroprotective protein: a novel gene essential for brain formation. Brain Res 144:83–90

    Article  CAS  Google Scholar 

  • Poggi SH, Goodwin K, Hill JM, Brenneman DE, Tendi E, Schinelli S, Abebe D, Spong CY (2003) The role of activity-dependent neuroprotective protein in a mouse model of fetal alcohol syndrome. Am J Obstet Gynecol 189:790–793

    Article  PubMed  CAS  Google Scholar 

  • Quinn JP, Bubb VJ, Marshall-Jones ZV, Coulson JM (2002) Neuron restrictive silencer factor as a modulator of neuropeptide gene expression. Regul Pept 108:135–141

    Article  PubMed  CAS  Google Scholar 

  • Rosenfeld N, Elowitz MB, Alon U (2002) Negative autoregulation speeds the response times of transcription networks. J Mol Biol 323:785–793

    Article  PubMed  CAS  Google Scholar 

  • Spencer EM, Chandler KE, Haddley K et al (2006) Regulation and role of REST and REST4 variants in modulation of gene expression in in vivo and in vitro in epilepsy models. Neurobiol Dis 24:41–52

    Article  PubMed  CAS  Google Scholar 

  • Spong CY, Abebe DT, Gozes I, Brenneman DE, Hill JM (2001) Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome. J Pharmacol Exp Ther 297:774–779

    PubMed  CAS  Google Scholar 

  • Steingart RA, Gozes I (2006) Recombinant activity-dependent neuroprotective protein protects cells against oxidative stress. Mol Cell Endocrinol 252:148–153

    Article  PubMed  CAS  Google Scholar 

  • Vulih-Shultzman I, Pinhasov A, Mandel S, Grigoriadis N, Touloumi O, Pittel Z, Gozes I (2007) Activity-dependent neuroprotective protein snippet NAP reduces tau hyperphosphorylation and enhances learning in a novel transgenic mouse model. J Pharmacol Exp Ther 323:438–449

    Article  PubMed  CAS  Google Scholar 

  • Zaltzman R, Alexandrovich A, Beni SM, Trembovler V, Shohami E, Gozes I (2004) Brain injury-dependent expression of activity-dependent neuroprotective protein. J Mol Neurosci 24:181–187

    Article  PubMed  CAS  Google Scholar 

  • Zaltzman R, Alexandrovich A, Trembovler V, Shohami E, Gozes I (2005) The influence of the peptide NAP on Mac-1-deficient mice following closed head injury. Peptides 26:1520–1527

    Article  PubMed  CAS  Google Scholar 

  • Zamostiano R, Pinhasov A, Gelber E et al (2001) Cloning and characterization of the human activity-dependent neuroprotective protein. J Biol Chem 276:708–714

    Article  PubMed  CAS  Google Scholar 

  • Zemlyak I, Furman S, Brenneman DE, Gozes I (2000) A novel peptide prevents death in enriched neuronal cultures. Regul Pept 96:39–43

    Article  PubMed  CAS  Google Scholar 

  • Zemlyak I, Manley N, Vulih-Shultzman I, Cutler AB, Graber K, Sapolsky RM, Gozes I (2009) The microtubule interacting drug candidate NAP protects against kainic acid toxicity in a rat model of epilepsy. J Neurochem 111:1252–1263

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Funding from the BBSRC (ASV, KH, VJB and JPQ) and a studentship from the University of Taibah, Kingdom of Saudi Arabia (MSA) supported this work. We thank DNA Sequencing & Services (MRCPPU, College of Life Sciences, University of Dundee, Scotland, www.dnaseq.co.uk) for DNA sequencing and Dr. Fahad Ali for helpful discussions during this work.

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Correspondence to Vivien J. Bubb.

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Moutasem S. Aboonq and Sylvia A. Vasiliou contributed equally to this work

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Aboonq, M.S., Vasiliou, S.A., Haddley, K. et al. Activity-Dependent Neuroprotective Protein Modulates Its Own Gene Expression. J Mol Neurosci 46, 33–39 (2012). https://doi.org/10.1007/s12031-011-9562-y

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  • DOI: https://doi.org/10.1007/s12031-011-9562-y

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