ABCC6 as a target in pseudoxanthoma elasticum

Current Drug Targets

Volumn 12, Issue 5, 2011, Pages 671-682

  Váradi, András ^a   Szabó, Zalán ^a   Pomozi, Viola ^a   de Boussac, Hugues ^a   Fülöp, Krisztina ^a   Arányi, Tamás ^a  

^a INSTITUTE OF ENZYMOLOGY   (Hungary)

Author keywords

Calcification; Cardiovascular; Connective tissue; Genetic disease; Homology model; Membrane proteins; Transcriptional regulation; Vitamin K

Indexed keywords

ABC TRANSPORTER; AMINOGLYCOSIDE; CALCIUM; GAMMA INTERFERON; MULTIDRUG RESISTANCE PROTEIN 6; N ETHYLMALEIMIDE SENSITIVE FACTOR; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN; VITAMIN K GROUP;

ACUTE HEART INFARCTION; ANGINA PECTORIS; AXILLA; BINDING SITE; BRUCH MEMBRANE; CHROMOSOME 16; CHROMOSOME REARRANGEMENT; CODON; CORONARY ARTERY DISEASE; DNA METHYLATION; GENE EXPRESSION; GENE MUTATION; GENE STRUCTURE; GENE TARGETING; GENETIC HETEROGENEITY; GENETIC RISK; HISTOPATHOLOGY; HUMAN; HYPERTENSION; INGUINAL REGION; INTERMITTENT CLAUDICATION; MITRAL VALVE PROLAPSE; MOLECULAR MECHANICS; NONHUMAN; OXIDATIVE STRESS; PIGMENT EPITHELIUM; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN INTERACTION; PSEUDOXANTHOMA ELASTICUM; REPORTER GENE; RESTRICTIVE CARDIOMYOPATHY; REVIEW; STROKE; SUBRETINAL NEOVASCULARIZATION;

ALLELES; ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; DISEASE MODELS, ANIMAL; GENE THERAPY; HUMANS; MICE; MOLECULAR TARGETED THERAPY; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; MUTATION; PSEUDOXANTHOMA ELASTICUM; VITAMIN K;

EID: 79953323686     PISSN: 13894501     EISSN: None     Source Type: Journal    
DOI: 10.2174/138945011795378612     Document Type: Review

References (118)

1. Rigal D. Observations pour servir á l'histoire de la cheloide diffuse xantholasmique. Ann Derm Syph 1881; 21: 491-501.
2. Darier J. Pseudoxanthoma elasticum. Monatshefte Prakt Derm 1896; 23: 609-17.
3. Grönblad E. Angioid streaks--pseudoxanthoma elasticum. Acta Ophthal 1929; 7: 329.
4. Hu X, Plomp AS, van SS, Wijnholds J, de Jong PT, Bergen AA. Pseudoxanthoma elasticum: a clinical, histopathological, and molecular update. Surv Ophthalmol 2003; 48: 424-38.
5. Walker ER, Frederickson RG, Mayes MD. The mineralization of elastic fibers and alterations of extracellular matrix in pseudoxanthoma elasticum. Ultrastructure, immunocytochemistry, and X-ray analysis. Arch Dermatol 1989; 125: 70-6.
6. Baccarani-Contri M, Vincenzi D, Cicchetti F, Mori G, Pasquali-Ronchetti I. Immunochemical identification of abnormal constituents in the dermis of pseudoxanthoma elasticum patients. Eur J Histochem 1994; 38: 111-23.
7. Limas C. Late onset focal dermal elastosis: a distinct clinicopathologic entity? Am J Dermatopathol 1999; 21: 381-3.
8. Choi GS, Kang DS, Chung JJ, Lee MG. Osteoma cutis coexisting with cutis laxa-like pseudoxanthoma elasticum. J Am Acad Dermatol 2000; 43: 337-9.
9. Nikko AP, Dunningan M, Cockerell CJ. Calciphylaxis with histologic changes of pseudoxanthoma elasticum. Am J Dermatopathol 1996; 18: 396-9.
10. Gross G. Osteitis deformans (Paget)--angioid streaks (Knapp)--pseudoxanthoma elasticum (Darier)--manifestations of a common systemic disease?. Arch Orthop Unfallchir 1959; 50: 613-7.
11. Vanakker OM, Martin L, Gheduzzi D, et al. Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity. J Invest Dermatol 2007; 127: 581-7.
12. Finger RP, Charbel IP, Ladewig MS, et al. Pseudoxanthoma elasticum: genetics, clinical manifestations and therapeutic approaches. Surv Ophthalmol 2009; 54: 272-85.
13. Dreyer R, Green WR. The pathology of angioid streaks: a study of twenty-one cases. Trans Pa Acad Ophthalmol Otolaryngol 1978; 31: 158-67.
14. Lim JI, Bressler NM, Marsh MJ, Bressler SB. Laser treatment of choroidal neovascularization in patients with angioid streaks. Am J Ophthalmol 1993; 116: 414-23.
15. Pece A, Avanza P, Galli L, Brancato R. Laser photocoagulation of choroidal neovascularization in angioid streaks. Retina 1997; 17: 12-6.
16. Gragoudas ES, Adamis AP, Cunningham ET, Jr., Feinsod M, Guyer DR. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 2004; 351: 2805-16.
17. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006; 355: 1419-31.
18. Finger RP, Charbel IP, Ladewig M, Holz FG, Scholl HP. Intravitreal bevacizumab for choroidal neovascularisation associated with pseudoxanthoma elasticum. Br J Ophthalmol 2008; 92: 483-7.
19. Navarro-Lopez F, Llorian A, Ferrer-Roca O, Betriu A, Sanz G. Restrictive cardiomyopathy in pseudoxanthoma elasticum. Chest 1980; 78: 113-5.
20. Przybojewski JZ, Maritz F, Tiedt FA, van der Walt JJ. Pseudoxanthoma elasticum with cardiac involvement. A case report and review of the literature. S Afr Med J 1981; 59: 268-75.
21. Challenor VF, Conway N, Monro JL. The surgical treatment of restrictive cardiomyopathy in pseudoxanthoma elasticum. Br Heart J 1988; 59: 266-9.
22. Fukuda K, Uno K, Fujii T, Mukai M, Handa S. Mitral stenosis in pseudoxanthoma elasticum. Chest 1992; 101: 1706-7.
23. Lebwohl M, Halperin J, Phelps RG. Brief report: occult pseudoxanthoma elasticum in patients with premature cardiovascular disease. N Engl J Med 1993; 329: 1237-9.
24. Fah L. [Pseudoxanthoma elasticum--a visual diagnosis]. Schweiz Med Wochenschr 1991; 121: 660-3.
25. Trip MD, Smulders YM, Wegman JJ, et al. Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease. Circulation 2002; 106: 773-5.
26. Koblos G, Andrikovics H, Prohaszka Z, Tordai A, Varadi A, Aranyi T. The R1141X loss-of-function mutation of the ABCC6 gene is a strong genetic risk factor for coronary artery disease. Genet Test Mol Biomarkers 2010; 14: 75-8.
27. Le Saux O, Urban Z, Tschuch C, et al. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet 2000; 25: 223-7.
28. Bergen AA, Plomp AS, Schuurman EJ, et al. Mutations in ABCC6 cause pseudoxanthoma elasticum. Nat Genet 2000; 25: 228-31.
29. Ringpfeil F, Lebwohl MG, Christiano AM, Uitto J. Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc Natl Acad Sci USA 2000; 97: 6001-6.
30. Pulkkinen L, Nakano A, Ringpfeil F, Uitto J. Identification of ABCC6 pseudogenes on human chromosome 16p: implications for mutation detection in pseudoxanthoma elasticum. Hum Genet 2001; 109: 356-65.
31. Symmons O, Varadi A, Aranyi T. How segmental duplications shape our genome: recent evolution of ABCC6 and PKD1 Mendelian disease genes. Mol Biol Evol 2008; 25: 2601-13.
32. Cai L, Struk B, Adams MD, et al. A 500-kb region on chromosome 16p13.1 contains the pseudoxanthoma elasticum locus: high-resolution mapping and genomic structure. J Mol Med 2000; 78: 36-46.
33. Dauwerse JG, Wessels JW, Giles RH, et al. Cloning the breakpoint cluster region of the inv(16) in acute nonlymphocytic leukemia M4 Eo. Hum Mol Genet 1993; 2: 1527-34.
34. van Dongen JJ, Macintyre EA, Gabert JA, et al. Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia. Leukemia 1999; 13: 1901-28.
35. Buys TP, Chari R, Lee EH, et al. Genetic changes in the evolution of multidrug resistance for cultured human ovarian cancer cells. Genes Chromosomes Cancer 2007; 46: 1069-79.
36. Aranyi T, Ratajewski M, Bardoczy V, et al. Identification of a DNA methylation-dependent activator sequence in the pseudoxanthoma elasticum gene, ABCC6. J Biol Chem 2005; 280: 18643-50.
37. Aranyi T, Faucheux BA, Khalfallah O, et al. The tissue-specific methylation of the human tyrosine hydroxylase gene reveals new regulatory elements in the first exon. J Neurochem 2005; 94: 129-39.
38. Ratajewski M, Van de Ven WJ, Bartosz G, Pulaski L. The human pseudoxanthoma elasticum gene ABCC6 is transcriptionally regulated by PLAG family transcription factors. Hum Genet 2008; 124: 451-63.
39. Ratajewski M, Bartosz G, Pulaski L. Expression of the human ABCC6 gene is induced by retinoids through the retinoid X receptor. Biochem Biophys Res Commun 2006; 350: 1082-7.
40. Jiang Q, Matsuzaki Y, Li K, Uitto J. Transcriptional regulation and characterization of the promoter region of the human ABCC6 gene. J Invest Dermatol 2006; 126: 325-35.
41. de Boussac H, Ratajewski M, Sachrajda I, et al. The ERK1/2-hepatocyte nuclear factor 4alpha axis regulates human ABCC6 gene expression in hepatocytes. J Biol Chem 2010; 285: 22800-8.
42. Bolotin E, Liao H, Ta TC, et al. Integrated approach for the identification of human hepatocyte nuclear factor 4alpha target genes using protein binding microarrays. Hepatology 2010; 51: 642-53.
43. Odom DT, Zizlsperger N, Gordon DB, et al. Control of pancreas and liver gene expression by HNF transcription factors. Science 2004; 303: 1378-81.
44. Sladek FM, Zhong WM, Lai E, Darnell JE, Jr. Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev 1990; 4: 2353-65.
45. Kool M, van der LM, de HM, Baas F, Borst P. Expression of human MRP6, a homologue of the multidrug resistance protein gene MRP1, in tissues and cancer cells. Cancer Res 1999; 59: 175-82.
46. Ratajewski M, de Boussac H, Sachrajda I, et al. A strong primate-and tissue-specific enhancer located in the first intron of ABCC6 gene is regulated by CCAAT/Enhancer binding protein. Biochemical J 2011; Submitted.
47. Li Q, Jiang Q, Pfendner E, Varadi A, Uitto J. Pseudoxanthoma elasticum: clinical phenotypes, molecular genetics and putative pathomechanisms. Exp Dermatol 2009; 18: 1-11.
48. Hamlin N, Beck K, Bacchelli B, Cianciulli P, Pasquali-Ronchetti I, Le Saux O. Acquired Pseudoxanthoma elasticum-like syndrome in beta-thalassaemia patients. Br J Haematol 2003; 122: 852-4.
49. Edinger C, Bollt O, Le Saux O. Tissue-specific down regulation of ABCC6 expression in beta-thalassemia mice. Ethnic Dis 2009; 19: 63-4.
50. Schulz V, Hendig D, Henjakovic M, Szliska C, Kleesiek K, Gotting C. Mutational analysis of the ABCC6 gene and the proximal ABCC6 gene promoter in German patients with pseudoxanthoma elasticum (PXE). Hum Mutat 2006; 27: 831.
51. Hendig D, Arndt M, Szliska C, Kleesiek K, Gotting C. SPP1 promoter polymorphisms: identification of the first modifier gene for pseudoxanthoma elasticum. Clin Chem 2007; 53: 829-36.
52. Zarbock R, Hendig D, Szliska C, Kleesiek K, Gotting C. Pseudoxanthoma elasticum: genetic variations in antioxidant genes are risk factors for early disease onset. Clin Chem 2007; 53: 1734-40.
53. Zarbock R, Hendig D, Szliska C, Kleesiek K, Gotting C. Vascular endothelial growth factor gene polymorphisms as prognostic markers for ocular manifestations in pseudoxanthoma elasticum. Hum Mol Genet 2009; 18: 3344-51.
54. Schon S, Schulz V, Prante C, et al. Polymorphisms in the xylosyltransferase genes cause higher serum XT-I activity in patients with pseudoxanthoma elasticum (PXE) and are involved in a severe disease course. J Med Genet 2006; 43: 745-9.
55. Ilias A, Urban Z, Seidl TL, et al. Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). J Biol Chem 2002; 277: 16860-7.
56. Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD. Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res 2002; 62: 6172-7.
57. Madon J, Hagenbuch B, Landmann L, Meier PJ, Stieger B. Transport function and hepatocellular localization of mrp6 in rat liver. Mol Pharmacol 2000; 57: 634-41.
58. Fulop K, Barna L, Symmons O, Zavodszky P, Varadi A. Clustering of disease-causing mutations on the domain-domain interfaces of ABCC6. Biochem Biophys Res Commun 2009; 379: 706-9.
59. Dawson RJ, Hollenstein K, Locher KP. Uptake or extrusion: crystal structures of full ABC transporters suggest a common mechanism. Mol Microbiol 2007; 65: 250-7.
60. Dawson RJ, Locher KP. Structure of a bacterial multidrug ABC transporter. Nature 2006; 443: 180-5.
61. Aller SG, Yu J, Ward A, et al. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 2009; 323: 1718-22.
62. Smith PC, Karpowich N, Millen L, et al. ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer. Mol Cell 2002; 10: 139-49.
63. Klement JF, Matsuzaki Y, Jiang QJ, et al. Targeted ablation of the abcc6 gene results in ectopic mineralization of connective tissues. Mol Cell Biol 2005; 25: 8299-310.
64. Gorgels TG, Hu X, Scheffer GL, et al. Disruption of Abcc6 in the mouse: novel insight in the pathogenesis of pseudoxanthoma elasticum. Hum Mol Genet 2005; 14: 1763-73.
65. Meng H, Vera I, Che N, et al. Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics. Proc Natl Acad Sci USA 2007; 104: 4530-5.
66. Aherrahrou Z, Doehring LC, Ehlers EM, Liptau H, Depping R, Linsel-Nitschke P, et al. An alternative splice variant in Abcc6, the gene causing dystrophic calcification, leads to protein deficiency in C3H/He mice. J Biol Chem 2008; 283: 7608-15.
67. Li Q, Sadowski S, Frank M, et al. The Abcc6a gene expression is required for normal zebrafish development. J Invest Dermatol 2010; 130: 2561-8.
68. Uitto J, Pulkkinen L, Ringpfeil F. Molecular genetics of pseudoxanthoma elasticum: a metabolic disorder at the environment-genome interface? Trends Mol Med 2001; 7: 13-7.
69. Jiang Q, Endo M, Dibra F, Wang K, Uitto J. Pseudoxanthoma elasticum is a metabolic disease. J Invest Dermatol 2009; 129: 348-54.
70. Jiang Q, Oldenburg R, Otsuru S, Grand-Pierre AE, Horwitz EM, Uitto J. Parabiotic heterogenetic pairing of abcc6-/-/rag1-/- mice and their wild-type counterparts halts ectopic mineralization in a murine model of pseudoxanthoma elasticum. Am J Pathol 2010; 176: 1855-62.
71. Macmillan DC, Vickers HR. Pseudoxanthoma elasticum and a coagulation defect. Br J Dermatol 1971; 84: 182.
72. Rongioletti F, Bertamino R, Rebora A. Generalized pseudoxanthoma elasticum with deficiency of vitamin K-dependent clotting factors. J Am Acad Dermatol 1989; 21: 1150-2.
73. Le Corvaisier-Pieto C, Joly P, Thomine E, Lair G, Lauret P. [Generalized pseudoxanthoma elasticum combined with vitamin K dependent clotting factors deficiency]. Ann Dermatol Venereol 1996; 123: 555-8.
74. Berkner KL. Vitamin K-dependent carboxylation. Vitam Horm 2008; 78: 131-56.
75. Oldenburg J, Marinova M, Muller-Reible C, Watzka M. The vitamin K cycle. Vitam Horm 2008; 78: 35-62.
76. Schurgers LJ, Teunissen KJ, Knapen MH, et al. Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification. Arterioscler Thromb Vasc Biol 2005; 25: 1629-33.
77. Schurgers LJ, Spronk HM, Skepper JN, et al. Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. J Thromb Haemost 2007; 5: 2503-11.
78. Schurgers LJ, Cranenburg EC, Vermeer C. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost 2008; 100: 593-603.
79. Jiang Q, Li Q, Uitto J. Aberrant mineralization of connective tissues in a mouse model of pseudoxanthoma elasticum: systemic and local regulatory factors. J Invest Dermatol 2007; 127: 1392-402.
80. Li Q, Jiang Q, Schurgers LJ, Uitto J. Pseudoxanthoma elasticum: reduced gamma-glutamyl carboxylation of matrix gla protein in a mouse model (Abcc6-/-). Biochem Biophys Res Commun 2007; 364: 208-13.
81. Gheduzzi D, Boraldi F, Annovi G, et al. Matrix Gla protein is involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients. Lab Invest 2007; 87: 998-1008.
82. Vanakker OM, Martin L, Schurgers LJ, et al. Low serum vitamin K in PXE results in defective carboxylation of mineralization inhibitors similar to the GGCX mutations in the PXE-like syndrome. Lab Invest 2010; 90: 895-905.
83. Borst P, van de WK, Schlingemann R. Does the absence of ABCC6 (multidrug resistance protein 6) in patients with Pseudoxanthoma elasticum prevent the liver from providing sufficient vitamin K to the periphery? Cell Cycle 2008; 7: 1575-9.
84. Li J, Lin JC, Wang H, et al. Novel role of vitamin k in preventing oxidative injury to developing oligodendrocytes and neurons. J Neurosci 2003; 23: 5816-26.
85. Garcia-Fernandez MI, Gheduzzi D, Boraldi F, et al. Parameters of oxidative stress are present in the circulation of PXE patients. Biochim Biophys Acta 2008; 1782: 474-81.
86. Li Q, Jiang Q, Uitto J. Pseudoxanthoma elasticum: oxidative stress and antioxidant diet in a mouse model (Abcc6-/-). J Invest Dermatol 2008; 128: 1160-4.
87. Thijssen HH, Vervoort LM, Schurgers LJ, Shearer MJ. Menadione is a metabolite of oral vitamin K. Br J Nutr 2006; 95: 260-6.
88. Okano T, Shimomura Y, Yamane M, et al. Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice. J Biol Chem 2008; 283: 11270-9.
89. Harrington DJ, Soper R, Edwards C, Savidge GF, Hodges SJ, Shearer MJ. Determination of the urinary aglycone metabolites of vitamin K by HPLC with redox-mode electrochemical detection. J Lipid Res 2005; 46: 1053-60.
90. Jiang Q, Li Q, Grand-Pierre AE, Schurgers LJ, Uitto J. Administration of Vitamin K Does Not Counteract the Ectopic Mineralization of Connective Tissues in Abcc6-/- Mice, a Model for Pseudoxanthoma Elasticum. Cell Cycle 2011; 10: 701-7.
91. Brampton C, Yamaguchi Y, Vanakker OM, et al. An increase in dietary vitamin K does not prevent soft tissue mineralization in a mouse model of PXE. Cell Cycle 2011; submitted.
92. Hendig D, Langmann T, Kocken S, et al. Gene expression profiling of ABC transporters in dermal fibroblasts of pseudoxanthoma elasticum patients identifies new candidates involved in PXE pathogenesis. Lab Invest 2008; 88: 1303-15.
93. Beck K, Hayashi K, Dang K, Hayashi M, Boyd CD. Analysis of ABCC6 (MRP6) in normal human tissues. Histochem Cell Biol 2005; 123: 517-28.
94. Boraldi F, Quaglino D, Croce MA, et al. Multidrug resistance protein-6 (MRP6) in human dermal fibroblasts. Comparison between cells from normal subjects and from Pseudoxanthoma elasticum patients. Matrix Biol 2003; 22: 491-500.
95. Vanakker OM, Leroy BP, Coucke P, et al. Novel clinico-molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart. Hum Mutat 2008; 29: 205.
96. Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 2002; 298: 1911-2.
97. Sugden PH, Clerk A. Regulation of the ERK subgroup of MAP kinase cascades through G protein-coupled receptors. Cell Signal 1997; 9: 337-51.
98. Junttila MR, Li SP, Westermarck J. Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival. FASEB J 2008; 22: 954-65.
99. Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 2007; 26: 3291-310.
100. Friday BB, Adjei AA. Advances in targeting the Ras/Raf/MEK/Erk mitogen-activated protein kinase cascade with MEK inhibitors for cancer therapy. Clin Cancer Res 2008; 14: 342-6.
101. Pasquali-Ronchetti I, Garcia-Fernandez MI, Boraldi F, et al. Oxidative stress in fibroblasts from patients with pseudoxanthoma elasticum: possible role in the pathogenesis of clinical manifestations. J Pathol 2006; 208: 54-61.
102. Reddy S, Yang W, Taylor DG, et al. Mitogen-activated protein kinase regulates transcription of the ApoCIII gene. Involvement of the orphan nuclear receptor HNF4. J Biol Chem 1999; 274: 33050-6.
103. Hatzis P, Kyrmizi I, Talianidis I. Mitogen-activated protein kinase-mediated disruption of enhancer-promoter communication inhibits hepatocyte nuclear factor 4alpha expression. Mol Cell Biol 2006; 26: 7017-29.
104. Xie X, Liao H, Dang H, et al. Down-regulation of hepatic HNF4alpha gene expression during hyperinsulinemia via SREBPs. Mol Endocrinol 2009; 23: 434-43.
105. Martinez-Jimenez CP, Kyrmizi I, Cardot P, Gonzalez FJ, Talianidis I. HNF4{alpha} coordinates a transcription factor network regulating hepatic fatty acid metabolism. Mol Cell Biol 2010; 30: 565-77.
106. Bailly A, Torres-Padilla ME, Tinel AP, Weiss MC. An enhancer element 6 kb upstream of the mouse HNF4alpha1 promoter is activated by glucocorticoids and liver-enriched transcription factors. Nucleic Acids Res 2001; 29: 3495-505.
107. Hayashi H, Sugiyama Y. 4-phenylbutyrate enhances the cell surface expression and the transport capacity of wild-type and mutated bile salt export pumps. Hepatology 2007; 45: 1506-16.
108. Loo TW, Clarke DM. Correction of defective protein kinesis of human P-glycoprotein mutants by substrates and modulators. J Biol Chem 1997; 272: 709-12.
109. Egan ME, Pearson M, Weiner SA, et al. Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 2004; 304: 600-2.
110. Rubenstein RC, Egan ME, Zeitlin PL. In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR. J Clin Invest 1997; 100: 2457-65.
111. Rubenstein RC, Zeitlin PL. Sodium 4-phenylbutyrate downregu-lates Hsc70: implications for intracellular trafficking of DeltaF508-CFTR. Am J Physiol Cell Physiol 2000; 278: C259-67.
112. Rubenstein RC, Zeitlin PL. A pilot clinical trial of oral sodium 4-phenylbutyrate (Buphenyl) in deltaF508-homozygous cystic fibro-sis patients: partial restoration of nasal epithelial CFTR function. Am J Respir Crit Care Med 1998; 157: 484-90.
113. Batshaw ML, MacArthur RB, Tuchman M. Alternative pathway therapy for urea cycle disorders: twenty years later. J Pediatr 2001; 138: S46-S54.
114. Yam GH, Gaplovska-Kysela K, Zuber C, Roth J. Sodium 4-phenyl-butyrate acts as a chemical chaperone on misfolded myocilin to rescue cells from endoplasmic reticulum stress and apoptosis. Invest Ophthalmol Vis Sci 2007; 48: 1683-90.
115. Le Saux O, Fülöp K, Yamaguchi Y, et al. Assisted maturation of human ABCC6 disease causing mutants in mouse liver. Hepatology 2011; submitted.
116. Barton-Davis ER, Cordier L, Shoturma DI, Leland SE, Sweeney HL. Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. J Clin Invest 1999; 104: 375-81.
117. Xi B, Guan F, Lawrence DS. Enhanced production of functional proteins from defective genes. J Am Chem Soc 2004; 126: 5660-1.
118. Welch EM, Barton ER, Zhuo J, et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature 2007; 447: 87-91.