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In vitro studies of PHOX2B gene mutations in congenital central hypoventilation syndrome

  • Tiziana Bachetti
  • Isabella Ceccherini

Keywords

Mutant Protein Frameshift Mutation Heat Shock Response Oculopharyngeal Muscular Dystrophy PHOX2B Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Abu-Baker A, Messaed C, Laganiere J, Gaspar C, Brais B, Rouleau GA (2003) Involvement of the ubiquitin-proteasome pathway and molecular chaperones in oculopharyngeal muscular dystrophy. Hum Mol Genet 12: 2609-2623PubMedCrossRefGoogle Scholar
  2. 2.
    Adachi M, Browne D, Lewis EJ (2000) Paired-like homeodomain proteins Phox2a/Arix and Phox2b/NBPhox have similar genetic organization and independently regulate dopamine beta-hydroxylase gene transcription. DNA Cell Biol 19: 539-554PubMedCrossRefGoogle Scholar
  3. 3.
    Albrecht AN, Kornak U, Boddrich A, Suring K, Robinson PN, Stiege AC, Lurz R, Stricker S, Wanker EE, Mundlos S (2004) A molecular pathogenesis for transcription factor associated polyalanine tract expansions. Hum Mol Genet 13: 2351-2359PubMedCrossRefGoogle Scholar
  4. 4.
    Amiel J, Laudier B, Attié-Bitach T, Trang H, De Pontual L, Gener B, Trochet D, Etchevers H, Ray P, Simonneau M, Vekemans M, Munnich A, Gaultier C, Lyon-net S (2003) Polyalanine expansion and frameshift mutations of the paired like homeobox gene PHOX2B in congenital central hypoventilation syndrome. Nat Genet 33: 459-461PubMedCrossRefGoogle Scholar
  5. 5.
    Bachetti T, Bocca P, Borghini S, Matera I, Prigione I, Ravazzolo R, Ceccherini I (2006) Geldanamycin promotes nuclear localisation and clearance of PHOX2B misfolded proteins containing polyalanine expansions. Int J Biochem Cell BiolGoogle Scholar
  6. 6.
    Bachetti T, Matera I, Borghini S, Di Duca M, Ravazzolo R, Ceccherini I (2005) Distinct pathogenesis mechanisms for PHOX2B associated polyalanine expansions and frameshift mutations in Congenital Central Hypoventilation Syndrome. Hum Mol Genet 14: 1815-1824PubMedCrossRefGoogle Scholar
  7. 7.
    Berry-Kravis EM, Zhoul L, Rand CM, Weese-Mayer D (2006) Congenital Central Hypoventilation Syndrome: PHOX2B mutations and phenotype. Am J Respir Crit Care Med 174: 1139-1144PubMedCrossRefGoogle Scholar
  8. 8.
    Borghini S, Bachetti T, Fava M, Di Duca M, Cargnin F, Fornasari D, Ravazzolo R, Ceccherini I (2006) The TLX-2 homeobox gene is a transcriptional target of PHOX2B in neural-crest-derived cells. Biochem J 395: 355-361PubMedCrossRefGoogle Scholar
  9. 9.
    Brown LY, Brown SA (2004) Alanine tracts: the expanding story of human illness and trinucleotide repeats. Trends Genet 20: 51-58PubMedCrossRefGoogle Scholar
  10. 10.
    Brown L, Paraso M, Arkell R, Brown S (2005) In vitro analysis of partial loss-offunction ZIC-2 mutations in Holoprosencephaly: alanine tract expansion modulates DNA binding and transactivation. Hum Mol Genet 14: 411-420PubMedCrossRefGoogle Scholar
  11. 11.
    Brunet JF, Pattyn A (2002) Phox2 genes – from patterning to connectivity. Curr Opin Genet Dev 12: 435-440PubMedCrossRefGoogle Scholar
  12. 12.
    Caburet S, Demarez A, Moumme L, Fellows M, De Baere E, Veitia RA (2004) A recurrent polyalanine expansion in the transcription factor FOXL2 induces extensive nuclear and cytoplasmic protein aggregation. J Med Genet 41: 931-946CrossRefGoogle Scholar
  13. 13.
    Davies JE, Sarkar S, Rubinsztein DC (2006) Trehalose reduces aggregate formation and delays pathology in a transgenic mouse model of oculopharyngeal muscular dystrophy. Hum Mol Genet 15: 23-31PubMedCrossRefGoogle Scholar
  14. 14.
    Flora A, Lucchetti H, Benfante R, Goridis C, Clementi F, Fornasari D (2001) Sp proteins and Phox2b regulate the expression of the human Phox2a gene. J Neurosci 21: 7037-7045PubMedGoogle Scholar
  15. 15.
    Holzinger A, Mittal RA, Kachel W, Priessmann H, Hammel M, Ihrler S, Till H, Münch H-G (2005) A novel 17 bp deletion in the PHOX2B gene causes congenital central hypoventilation syndrome with total aganglionosis of the small and large intestine. Am J Med Genet 139: 50-51CrossRefGoogle Scholar
  16. 16.
    Jana NR, Tanaka M, Wang G-H, Nukina N (2000) Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity. Hum Mol Genet 9: 2009-2018PubMedCrossRefGoogle Scholar
  17. 17.
    Layfield R, Cavey JR, Lowe J (2003) Role of ubiquitin-mediated proteolysis in the pathogenesis of neurodegenerative disorders. Ageing Res Rev 2: 343-356PubMedCrossRefGoogle Scholar
  18. 18.
    Lavoie H, Debeane F, Trinh O-D, Turcotte J-F, Corbeil-Girard L-P, Dicaire M-J, Saint-Denis A, Pagé M, Rouleau GA, Brais B (2003) Polymorphism, shared functions and convergent evolution of genes with sequences coding for polyalanine domains. Hum Mol Genet 12: 2967-2979PubMedCrossRefGoogle Scholar
  19. 19.
    Matera I, Bachetti T, Puppo F, Di Duca M, Morandi F, Casiraghi GM, Cilio MR, Hennekam R, Hofstra R, Schober JG, Ravazzolo R, Ottonello G, Ceccherini I (2004) PHOX2B mutations and polyalanine expansions correlate with the severity of the respiratory phenotype and associated symptoms in both congenital and late onset central hypoventilation syndrome. J Med Genet 41: 373-380PubMedCrossRefGoogle Scholar
  20. 20.
    Mosse YP, Laudenslager M, Khazi D, Carlisle AJ, Winter CL, Rappaport E, Maris JM (2004) Germline PHOX2B mutations in hereditary neuroblastoma. Am J Hum Genet 75: 727-730PubMedCrossRefGoogle Scholar
  21. 21.
    Nasrallah IM, Minarcik JC, Golden JA (2004) A polyalanine tract expansion in Arx forms intranuclear inclusions and results in increased cell death. J Cell Biol 167: 411-416PubMedCrossRefGoogle Scholar
  22. 22.
    Ravikumar B, Duden R, Rubinsztein DC (2002) Aggregated-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum Mol Genet 11: 1107-1117PubMedCrossRefGoogle Scholar
  23. 23.
    Sasaki A, Kanai M, Kijima K, Akaba K, Hashimoto M, Otaki S, Koizumi T, Kusuda S, Ogawa Y, Tuchiya K, Yamamoto W, Nakamura T, Hayasaka K (2003) Molecular analysis of congenital central hypoventilation syndrome. Hum Genet 114: 22-26PubMedCrossRefGoogle Scholar
  24. 24.
    Shintani T, Klionsky D (2004) Autophagy in health and disease: a double-edged sword. Science 306: 990-995PubMedCrossRefGoogle Scholar
  25. 25.
    Sittler A, Lurz R, Lueder G, Priller J, Hayer-Hartl MK, Hartl FU, Lehrach H, Wanker E (2001) Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington’s disease. Hum Mol Genet 12: 1307-1315CrossRefGoogle Scholar
  26. 26.
    Trochet D, Bourdeaut F, Janoueix-Lerosey I, Deville A, de Pontual L, Schleiermacher G, Coze C, Philip N, Frebourg T, Munnich A, Lyonnet S, Delattre O, Amiel J (2004) Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma. Am J Hum Genet 74: 761-764PubMedCrossRefGoogle Scholar
  27. 27.
    Trochet D, Hong SJ, Lim JK, Brunet JF, Munnich A, Kim KS, Goridis C, Amiel J (2005a) Molecular consequences of PHOX2B missense frameshift and alanine expansion mutations leading to autonomic dysfunction. Hum Mol Genet 14: 3697-3708CrossRefGoogle Scholar
  28. 28.
    Trochet D, O’Brien LM, Gozal D, Trang H, Nordenskjold A, Laudier B, Svensson PJ, Uhrig S, Cole T, Niemann S, Munnich A, Gaultier C, Lyonnet S, Amiel J (2005b) PHOX2B genotype allows for prediction of tumoral risk in congenital central hypoventilation syndrome. Am J Hum Genet 76: 421-426CrossRefGoogle Scholar
  29. 29.
    Van Limpt V, Schramm A, Lakeman A, Van Sluis P, Chan A, Van Noesel M, Baas F, Caron H, Eggert A, Versteeg R (2004) The Phox2b homeobox gene is mutated in sporadic neuroblastomas. Oncogene 23: 9280-9288PubMedGoogle Scholar
  30. 30.
    Visintin R, Amon A (2000) The nucleolus: the magician’s hat for cell cycle tricks. Curr Opin Cell Biol 12: 372-377PubMedCrossRefGoogle Scholar
  31. 31.
    Wang Q, Mosser DD, Bag J (2005) Induction of HSP70 expression and recruitment of HSC70 and HSP70 in the nucleus reduce aggregation of a polyalanine expansion mutant of PABPN1 in HeLa cells. Hum Mol Genet 14: 3673-3684PubMedCrossRefGoogle Scholar
  32. 32.
    Weese-Mayer DE, Berry-Kravis EM, Zhou L, Maher BS, Silvestri J-M, Curran ME, Marazita ML (2003) Idiopathic congenital central hypoventilation syndrome: analysis of genes pertinent to early autonomic nervous system embryologic development and identification of mutations in PHOX2B. Am J Med Genet 123: 267-278CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Tiziana Bachetti
    • 1
  • Isabella Ceccherini
    • 1
  1. 1.Laboratorio di Genetica MolecolareIstituto Giannina Gaslini – 16148Genova

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