Multiple Protein Domains Contribute to Nuclear Import and Cell Toxicity of DUX4, a Candidate Pathogenic Protein for Facioscapulohumeral Muscular Dystrophy

PLoS ONE

Volumn 8, Issue 10, 2013, Pages

  Corona, Edgardo Daniel ^a,c   Jacquelin, Daniela ^a   Gatica, Laura ^a   Rosa, Alberto Luis ^a,b  

^a Laboratorio de Biología Celular y Molecular   (Argentina)

^b Sanatorio Allende   (Argentina)

^c UNIVERSIDAD NACIONAL DE CÓRDOBA   (Argentina)

Author keywords

[No Author keywords available]

Indexed keywords

DOUBLE HOMEOBOX PROTEIN 4; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL DEATH; CELL NUCLEUS; CELLULAR DISTRIBUTION; CONTROLLED STUDY; CYTOPLASM; CYTOTOXICITY; DELETION MUTANT; FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY; HUMAN; HUMAN CELL; NUCLEAR IMPORT; NUCLEAR LOCALIZATION SIGNAL; PROTEIN DOMAIN; PROTEIN LOCALIZATION;

ACTIVE TRANSPORT, CELL NUCLEUS; CELL LINE, TUMOR; CELL NUCLEUS; HOMEODOMAIN PROTEINS; HUMANS; MUSCULAR DYSTROPHY, FACIOSCAPULOHUMERAL; MUTAGENESIS, SITE-DIRECTED;

EID: 84885137614     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0075614     Document Type: Article

References (44)

1. Hewitt JE, Lyle R, Clark LN, Valleley EM, Wright TJ, et al. (1994) Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy. Hum Mol Genet 3: 1287-1295.
2. Gabriels J, Beckers MC, Ding H, De Vriese A, Plaisance S, et al. (1999) Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element. Gene 236: 25-32.
3. Lyle R, Wright TJ, Clark LN, Hewitt JE, (1995) The FSHD associated repeat, D4Z4, is a member of a dispersed family of homeobox-containing repeats, subset of which are clustered on the short arms of the acrocentric chromosomes. Genomics 28: 389-397.
4. Clapp J, Mitchell LM, Bolland DJ, Fantes J, Corcoran AE, et al. (2007) Evolutionary conservation of a coding function for D4Z4, the tandem DNA repeat mutated in facioscapulohumeral muscular dystrophy. Am J Hum Genet 81: 264-279.
5. van Deutekom JC, Wijmenga C, van Tienhoven EA, Gruter AM, Hewitt JE, et al. (1993) FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit. Hum Mol Genet 2: 2037-2042.
6. Padberg GW (1998) Facioscapulohumeral muscular dystrophy. Neuromuscular Disorders: Clinical and Molecular Genetics. Chichester: John Wiley & Sons. 105 p.
7. Tawil R, Van Der Maarel SM, (2006) Facioscapulohumeral muscular dystrophy. Muscle Nerve 34: 1-15.
8. Tupler R, Berardinelli A, Barbierato L, Frants R, Hewitt JE, et al. (1996) Monosomy of distal 4q does not cause facioscapulohumeral muscular dystrophy. J Med Genet 33: 366-370.
9. Lemmers RJ, de Kievit P, Sandkuijl L, Padberg GW, van Ommen GJ, et al. (2002) Facioscapulohumeral muscular dystrophy is uniquely associated with one of the two variants of the 4q subtelomere. Nat Genet 32: 235-236.
10. van Overveld PG, Lemmers RJ, Sandkuijl LA, Enthoven L, Winokur ST, et al. (2003) Hypomethylation of D4Z4 in 4q-linked and non-4q-linked facioscapulohumeral muscular dystrophy. Nat Genet 5: 315-317.
11. de Greef JC, Lemmers RJ, Camaño P, Day JW, Sacconi S, et al. (2010) Clinical features of facioscapulohumeral muscular dystrophy 2. Neurology 75: 1548-1554.
12. Kowaljow V, Marcowytz A, Ansseau E, Conde C, Sauvage S, et al. (2007) The DUX4 gene at FSHD1A locus encodes a pro-apoptotic protein. Neuromuscul Disord 17: 611-623.
13. Snider L, Geng LN, Lemmers RJ, Kyba M, Ware CB, et al. (2010) Facioscapulohumeral dystrophy: incomplete suppression of a retrotransposed gene. PLoS Genet 6: e1001181.
14. Bosnakovski D, Xu Z, Gang EJ, Galindo CL, Liu M, et al. (2008) An isogenetic myoblast expression screen identifies DUX4-mediated FSHD-associated molecular pathologies. EMBO J 27: 2766-2779.
15. Vanderplanck C, Ansseau E, Charron S, Stricwant N, Tassin A, et al. (2011) The FSHD atrophic myotube phenotype is caused by DUX4 expression. PLoS One 6: e26820.
16. Wallace LM, Garwick SE, Mei W, Belayew A, Coppee F, et al. (2011) DUX4, a candidate gene for facioscapulohumeral muscular dystrophy, causes p53-dependent myopathy in vivo. Annals of neurology 69: 540-552.
17. Dixit M, Ansseau E, Tassin A, Winokur S, Shi R, et al. (2007) DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1. Proc Natl Acad Sci U S A 104: 18157-18162.
18. Geng LN, Yao Z, Snider L, Fong AP, Cech JN, et al. (2012) DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy. Dev Cell. 22: 38-51.
19. Wuebbles RD, Long SW, Hanel ML, Jones PL, (2010) Testing the effects of FSHD candidate gene expression in vertebrate muscle development. Int J Clin Exp Pathol 3: 386-400.
20. Lemmers RJ, van der Vliet PJ, Klooster R, Sacconi S, Camaño P, et al. (2010) A unifying genetic model for facioscapulohumeral muscular dystrophy. Science 329: 1650-1653.
21. Ostlund C, Garcia-Carrasquillo RM, Belayew A, Worman HJ, (2005) Intracellular trafficking and dynamics of double homeodomain proteins. Biochemistry 44: 2378-2384.
22. Offterdinger M, Schöfer C, Weipoltshammer K, Grunt TW, (2002) c-erbB-3: a nuclear protein in mammary epithelial cells. J Cell Biol 157: 929-939.
23. Paine PL, Moore LC, Horowitz SB, (1975) Nuclear envelope permeability. Nature 254: 109-114.
24. Mosammaparast N, Pemberton LF, (2004) Karyopherins: from nuclear-transport mediators to nuclear-function regulators. Trends Cell Biol 14: 547-556.
25. Dingwall C, Laskey RA, (1991) Nuclear targeting sequences-a consensus? Trends Biochem Sci 16: 478-481.
26. Robbins J, Dilworth SM, Laskey RA, Dingwall C, (1991) Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: identification of a class of bipartite nuclear targeting sequence. Cell 64: 615-623.
27. Goldfarb DS, Corbett AH, Mason DA, Harreman MT, Adam SA, (2004) Importin alpha: a multipurpose nuclear-transport receptor. Trends Cell Biol 14: 505-514.
28. Lange A, Mills RE, Lange CJ, Stewart M, Devine SE, et al. (2007) Classical nuclear localization signals: definition, function, and interaction with importin alpha. J Biol Chem 282: 5101-5105.
29. Kosugi S, Hasebe M, Entani T, Takayama S, Tomita M, et al. (2008) Design of peptide inhibitors for the importin alpha/beta nuclear import pathway by activity-based profiling. Chem Biol 15: 940-949.
30. Wilson DS, Sheng G, Jun S, Desplan C, (1996) Conservation and diversification in homeodomain-DNA interactions: a comparative genetic analysis. Proc Natl Acad Sci USA 93: 6886-6891.
31. Plaza S, Prince F, Adachi Y, Punzo C, Cribas DL, et al. (2008) Cross-regulatory protein-protein interactions between Hox and Pax transcription factors. Proc Natl Acad Sci USA 105: 13439-13444.
32. Christophe-Hobertus C, Duquesne V, Pichon B, Roger PP, Christophe D, (1999) Critical residues of the homeodomain involved in contacting DNA bases also specify the nuclear accumulation of thyroid transcription factor-1. Eur J Biochem 265: 491-497.
33. Kawamura-Saito M, Yamazaki Y, Kaneko K, Kawaguchi N, Kanda H, et al. (2006) Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation. Hum Mol Genet 15: 2125-2137.
34. Ansseau E, Laoudj-Chenivesse D, Marcowycz A, Tassin A, Vanderplanck C, et al. (2009) DUX4c is up-regulated in FSHD. It induces the MYF5 protein and human myoblast proliferation. PLoS One 4: e7482.
35. Dmitriev P, Lipinski M, Vassetzky YS, (2009) Pearls in the junk: dissecting the molecular pathogenesis of facioscapulohumeral muscular dystrophy. Neuromuscul Disord 19: 17-20.
36. Cabianca DS, Gabellini D, (2010) FSHD: copy number variations on the theme of muscular dystrophy. J Cell Biol 191: 1049-1060.
37. Chan SK, Mann RS, (1993) The segment identity functions of Ultrabithorax are contained within its homeo domain and carboxy-terminal sequences. Genes Dev 7: 796-811.
38. Briata P, Ilengo C, Bobola N, Corte G, (1999) Binding properties of the human homeodomain protein OTX2 to a DNA target sequence. FEBS Lett 445: 160-164.
39. Boulikas T, (1993) Nuclear localization signals. Crit Rev Eukaryot Gene Expr 3: 193-227.
40. Qian YQ, Furukubo-Tokunaga K, Resendez-Perez D, Müller M, Gehring WJ, et al. (1994) Nuclear magnetic resonance solution structure of the fushi tarazu homeodomain from Drosophila and comparison with the Antennapedia homeodomain. J Mol Biol 238: 333-345.
41. Tsao DH, Gruschus JM, Wang LH, Nirenberg M, Ferretti JA, (1995) The three-dimensional solution structure of the NK-2 homeodomain from Drosophila. J Mol Biol 251: 297-307.
42. Gehring WJ, Qian YQ, Billeter M, Furukubo-Tokunaga K, Schier AF, et al. (1994) Homeodomain-DNA recognition. Cell 78: 211-223.
43. Ades SE, Sauer RT, (1994) Differential DNA-binding specificity of the engrailed homeodomain: the role of residue 50. Biochemistry 33: 9187-8194.
44. LaCasse EC, Lefebvre YA, (1995) Nuclear localization signals overlap DNA- or RNA-binding domains in nucleic acid-binding proteins. Nucleic Acids Res 23: 1647-1656.