Roscovitine is a proteostasis regulator that corrects the trafficking defect of F508del-CFTR by a CDK-independent mechanism

British Journal of Pharmacology

Volumn 171, Issue 21, 2014, Pages 4831-4849

  Norez, C ^a   Vandebrouck, C ^a   Bertrand, J ^a   Noel, S ^a   Durieu, E ^b   Oumata, N ^c   Galons, H ^d   Antigny, F ^e   Chatelier, A ^a   Bois, P ^a   Meijer, L ^b,c   Becq, F ^a  

^a UNIVERSITÉ DE POITIERS   (France)

^b Protein Phosphorylation and Human Disease Group   (France)

^c Centre de Perharidy   (France)

^d UNIVERSITÉ PARIS DESCARTES   (France)

^e UNIVERSITY OF GENEVA MEDICAL SCHOOL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

1 [N,O BIS(5 ISOQUINOLINESULFONYL) N METHYLTYROSYL] 4 PHENYLPIPERAZINE; 2 MORPHOLINO 8 PHENYLCHROMONE; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; BREFELDIN; CALCIUM ION; CALNEXIN; CHELERYTHRINE; CYCLIN A; CYCLIN B; CYCLIN DEPENDENT KINASE; CYCLIN DEPENDENT KINASE 5; CYCLIN DEPENDENT KINASE 9; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DIMETHYL SULFOXIDE; GELDANAMYCIN; GLYCOGEN SYNTHASE KINASE 3; LACTACYSTIN; LUMACAFTOR; MIGLUSTAT; MITOGEN ACTIVATED PROTEIN KINASE 1; N (6 AMINOHEXYL) 5 CHLORO 1 NAPHTHALENESULFONAMIDE; N [2 (4 BROMOCINNAMYLAMINO)ETHYL] 5 ISOQUINOLINESULFONAMIDE; N6 METHYL ROSCOVITINE; O BENZYL ROSCOVITINE; OLOMOUCINE; PROTEASOME; ROSCOVITINE; THAPSIGARGIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VOLTAGE GATED SODIUM CHANNEL; CALCIUM; PROTEIN KINASE INHIBITOR; PURINE DERIVATIVE; SCN5A PROTEIN, HUMAN; SODIUM CHANNEL NAV1.5;

APOPTOSIS; ARTICLE; CALCIUM SIGNALING; CELL CULTURE; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYSTIC FIBROSIS; DRUG EFFICACY; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; ENDOPLASMIC RETICULUM; ENZYME INHIBITION; EPITHELIUM CELL; GENE DELETION; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE; IMMUNOPRECIPITATION; PATCH CLAMP TECHNIQUE; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN HOMEOSTASIS; PROTEIN PROTEIN INTERACTION; PROTEIN TRANSPORT; WESTERN BLOTTING; ANTAGONISTS AND INHIBITORS; CELL LINE; DRUG EFFECTS; GENETICS; HEK293 CELL LINE; METABOLISM; MUTATION;

CALCIUM; CELL LINE; CYCLIN-DEPENDENT KINASES; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; ENDOPLASMIC RETICULUM; EPITHELIAL CELLS; HEK293 CELLS; HUMANS; MUTATION; NAV1.5 VOLTAGE-GATED SODIUM CHANNEL; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN KINASE INHIBITORS; PROTEIN TRANSPORT; PURINES;

EID: 84918832154     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12859     Document Type: Article

References (118)

1. Aldoss IT, Tashi T, Ganti AK (2009). Seliciclib in malignancies. Expert Opin Investig Drugs 18: 1957-1965.
2. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M et al. (2013a). The Concise Guide to PHARMACOLOGY 2013/14:Ion channels. Br J Pharmacol 170: 1607-1651.
3. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M et al. (2013b). The Concise Guide to PHARMACOLOGY 2013/14: enzymes. Br J Pharmacol 170: 1797-1867.
4. Antigny F, Girardin N, Frieden M (2012). Transient receptor potential canonical channels are required for in vitro endothelial tube formation. J Biol Chem 287: 5917-5927.
5. Azakir BA, Di FS, Kinter J, Sinnreich M (2012). Proteasomal inhibition restores bio logical function of mis-sense mutated dysferlin in patient derived muscle cells. J Biol Chem 287: 10344-10354.
6. Bach S, Knockaert M, Reinhardt J, Lozach O, Schmitt S, Baratte B et al. (2005). Roscovitine targets, protein kinases and pyridoxal kinase. J Biol Chem 280: 31208-31219.
7. Bebok Z, Collawn JF, Wakefield J, Parker W, Li Y, Varga K et al. (2005). Failure of cAMP agonists to activate rescu ed deltaF508 CFTR in CFBE41o-Airway epithelial monolayers. J Physiol 569 (Pt 2): 601-615.
8. Becq F (2010). Cystic fibrosis transmembrane conductance regulator modulators for personalized drug treatment of cystic fibrosis: progress to date. Drugs 70: 241-259.
9. Benson C,White J,De BJ O'Donnell A,Raynaud F,Cruickshank C,et al. 2007 A phase I trial of the selective oral cyclin-dependent kinase inhibitor selicicli b (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days Br J Cancer 96, 29-37.
10. Bernier V, Bichet DG, Bouvier M (2004). Pharmacological chaperone action on G-protein-coupled receptors. Curr Opin Pharmacol 4: 528-533.
11. Bettayeb K, Oumata N, Echalier A, Ferandin Y, Endicott JA, Galons H et al. (2008). CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-depend ent kinases. Oncogene 27: 5797-5807.
12. Bettayeb K, Baunbae k D, Delehouze C, Loaëc N, Hole AJ, Baumli S et al. (2010). CDK inhibitors roscovitine and CR8 trigger Mcl-1 down-regulation and apoptotic cell death in neuroblastoma cells. Genes Cancer 1: 369-380.
13. Bradford MM (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254.
14. Bruscia E, Sangiuolo F, Sinibaldi P, Goncz KK, Novelli G, Gruenert DC (2002). Isolation of CF cell lines corrected at DeltaF508-CFTR locus by SFHR-mediated targeting. Gene Ther 9: 683-685.
15. Bukanov NO, Smith LA, Klinger KW, Ledbetter SR, Ibraghimov-Beskrovnaya O (2006). Long-lasting arrest of murine polycystic kidney disease with CDK inhibitor roscovitine. Nature 444: 949-952.
16. Canu N, Barbato C, Ciotti MT, Serafino A, Dus L, Calissano P (2000). Proteasome involvement and accumulation of ubiquitinated proteins in cerebellar granule neurons undergoing apoptosis. J Neurosci 20: 589-599.
17. Choi HS, Chung SH (2010). Roscovitine increases intracellular calcium release and capacitative calcium entry in PC12 cells. Neurosci Lett 469: 141-144.
18. Clancy JP, Rowe SM, Accurso FJ, Aitken ML, Amin RS, Ashlock MA et al. (2012). Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax 67: 12-18.
19. da Cruz FP, Newberry S, Jenkinson SF, Wormald MR, Butters TD, Alonzi DS et al. (2011). 4-C-Me-DAB and 4-C-Me-LAB-enantiomeric alkyl-branched pyrrolidine iminosugars-Are specific and potent ?-glucosidase inhibitors; acetone as the sole protecting group. Tetrahedron Lett 52: 219-223.
20. Denning GM, Anderson MP, Amara JF, Marshall J, Smith AE, Welsh MJ (1992). Processing of mutant cystic fibrosis transmembrane c onductance regulator is temperature-sensitive. Nature 358: 761-764.
21. Dormer RL, Harris CM, Clark Z, Pereira MM, Doull IJ, Norez C et al. (2005). Sildenafil (Viagra) corrects DeltaF508-CFTR lo cation in nasal epithelial cells from patients with cystic fibrosis. Thorax 60: 55-59.
22. Downey DG, Bell SC, Elborn JS (2009). Neutrophils in cystic fibrosis. Thorax 64: 81-88.
23. Egan ME, Glockner-Pagel J, Ambrose C, Cahill PA, Pappoe L, Balamuth N et al. (2002). Calcium-pump inhibitors induce functional surface expression of Delta F508-CFTR protein in cystic fibrosis epithelial cells. Nat M ed 8: 485-492.
24. Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glockner-Pagel J et al. (2004). Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 304: 600-602.
25. Ellgaard L, Helenius A (2003). Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4: 181-191.
26. Farinha CM, Amaral MD (2005). Most F508del-CFTR is targeted to degradation at an early folding checkpoint and independently of calnexin. Mol Cell Biol 25: 5242-5252.
27. Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL (1995). Inhibition of proteasom e activities and subunit-specific amino-terminal threonine modification by lactacystin. Science 268: 726-731.
28. Galietta LJ (2013). Managing the underlying cause of cystic fibrosis: a future role for potentiators and correctors. Paediatr Drugs 15: 393-402.
29. Galons H, Oumata N, Meijer L (2010). Cyclin-dependent kinase inhibitors: a survey of recent patent literature. Expert Opin Ther Pat 20: 377-404.
30. Ganapathi SB,Kester M,Elmslie KS 2009 State-dependent block of HERG potassium channels by R-roscovitine: im plications for cancer therapy Am J Physiol Cell Physiol 296, C701-C710.
31. Gong Q, Jones MA, Zhou Z (2006). Mechanisms of pharmacological rescue of trafficking-defective hERG mutant channels in human long QT syndrome. J Biol Chem 281: 4069-4074.
32. Gray NS, Wodicka L, Thunnissen AM, Norman TC, Kwon S, Espinoza FH et al. (1998). Exploiting chemical libraries, structure, and genomics in the search fo r kinase inhibitors. Science 281: 533-538.
33. Herczenik E, Gebbink MF (2008). Molecular and cellular aspects of protein misfolding and disease. FASEB J 22: 2115-2133.
34. Hsieh WS, Soo R, Peh BK, Loh T, Dong D, Soh D et al. (2009). Pharmacodynamic effects of seliciclib, an orally administered cell cycle modulator, in undifferentiated nasopharyngeal cancer. Clin Cancer Res 15: 1435-1442.
35. Hutt DM, Herman D, Rodrigues AP, Noel S, Pilewski JM, Matteson J et al. (2010). Reduced histone deacetylase 7 activity restores function to misfolded CFTR in cystic fibrosis. Nat Chem Biol 6: 25-33.
36. Jefferson DM, Valentich JD, Marini FC, Grubman SA, Iannuzzi MC, Dorkin HL et al. (1990). Expression of normal and cystic fibrosis phenotypes by continuous airway epithelial cell lines. Am J Physiol 259 (6 Pt 1): 496-505.
37. Jensen TJ, Loo MA, Pind S, Williams DB, Goldberg AL, Riordan JR (1995). Multiple proteolytic systems, including the proteasome, contribute to CFTR processing. Cell 83: 129-135.
38. Johnson LG, Mewshaw JP, Ni H, Friedmann T, Boucher RC, Olsen JC (1998). Effect of host modification and age on airway epithelial gene transfer mediated by a murine leukemia virus-derived vector. J Virol 72: 8861-8872.
39. Keller DI, Rougier JS, Kucera JP, Benammar N, Fressart V, Guicheney P et al. (2005). Brugada syndrome and fever: genetic and molecular characterization of patients carry ing SCN5A mutations. Cardiovasc Res 67: 510-519.
40. Knockaert M, Greengard P, Meijer L (2002). Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci 23: 417-425.
41. Li H, Findlay IA, Sheppard DN (2004). The relationship between cell proliferation, Cl-secretion, and renal cyst growth: a study using CFTR inhibitors. Kidney Int 66: 1926-1938.
42. Loo TW, Bartlett MC, Clarke DM (2004). Thapsigargin or curcumin does not promote maturation of processing mutants of the ABC transporters CFTR, and P-glycoprotein. Biochem Biophys Res Commun 325: 580-585.
43. Lubamba B, Lebacq J, Lebecque P, Vanbever R, Leonard A, Wallemacq P et al. (2009). Airway delivery of low-dose miglustat normalizes nasal potential difference in F508del cystic fibrosis mice. Am J Respir Crit C are Med 179: 1022-1028.
44. Lukacs GL, Verkman AS (2012). CFTR: folding, misfolding and correcting the DeltaF508 conformational defect. Trends Mol Med 18: 81-91.
45. Margolskee RF, McHendry-Rinde B, Horn R (1993). Panning transfected cells for electrophysiological studies. Biotechniques 15: 906-911.
46. Meijer L, Raymond E (2003). Roscovitine and other purines as kinase inhibitors. From starfish oocytes to clinical trials. Acc Chem Res 36: 417-425.
47. Meijer L, Borgne A, Mulner O, Chong JP, Blow JJ, Inagaki N et al. (1997). Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem 243: 527-536.
48. Mercie r A, Clément R, Harnois T, Bourmeyster N, Faivre JF, Findlay I et al. (2012). The ?1-subunit of Na(v)1.5 cardiac sodium channel is required for a dominant negative effect through ? interaction. PLoS ONE 7: e48690.
49. Meusser B, Hirsch C, Jarosch E, Sommer T (2005). ERAD: the long road to destruction. Nat Cell Biol 7: 766-772.
50. Moriceau S, Kantari C, Mocek J, Davezac N, Gabillet J, Guerrera IC et al. (2009). Coronin-1 is associated with neutrophil survival and is cleaved during apoptosis: potential implication in neutrophils from cystic fibrosis patients. J Immunol 182: 7254-7263.
51. Morice au S,Lenoir G,Witko-Sarsat V 2010 In cystic fibrosis homozygotes and heterozygotes, neutrophil apoptosis is delayed and modulated by diamide or roscovitine: evidence for an innate neutrophil disturbance. J Innate Immun 2, 260-266.
52. Norez C, Antigny F, Becq F, Vandebrouck C (2006a ). Maintaining low Ca2+ level in the endoplasmic reticulum restores abnormal endogenous F508del-CFTR trafficking in airway epithelial cells. Traffic 7: 562-573.
53. Norez C, Noel S, Wilke M, Bijvelds M, Jorna H, Melin P et al. (2006b ). Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the alpha-glucosidase inhibitor miglustat. FEBS Lett 580: 2081-2086.
54. Norez C, Bilan F, Kitzis A, Mettey Y, Becq F (2008). Proteasome-dependent pharmacological rescue of cystic fibrosis transmembrane conductance regulator revealed by mutatio n of glycine 622. J Pharmacol Exp Ther 325: 89-99.
55. Norez C, Antigny F, Noel S, Vandebrouck C, Becq F (2009). A cystic fibrosis respiratory epithelial cell chronically treated by miglustat acquires a non-cystic fibrosis-like phenotype. Am J Respir Cell Mol Biol 41: 217-225.
56. Dormer RL, Harris CM, Clark Z, Pereira MM, Doull IJ, Norez C et al. (2005). Sildenafil (Viagra) corrects DeltaF508-CFTR location in nasal epithelial cells from patients with cystic fibrosis. Thorax 60: 55-59.
57. Downey DG, Bell SC, Elborn JS (2009). Neutrophils in cystic fibrosis. Thorax 64: 81-88.
58. Egan ME, Glockner-Pagel J, Ambrose C, Cahill PA, Pappoe L, Balamuth N et al. (2002). Calcium-pump inhibitors induce functional surface expression of Delta F508-CFTR protein in cystic fibrosis epithelial cells. Nat Med 8: 485-492.
59. Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glockner-Pagel J et al. (2004). Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 304: 600-602.
60. Ellgaard L, Helenius A (2003). Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4: 181-191.
61. Farinha CM, Amaral MD (2005). Most F508del-CFTR is targeted to degradation at an early folding checkpoint and independently of calnexin. Mol Cell Biol 25: 5242-5252.
62. Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL (1995). Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science 268: 726-731.
63. Galietta LJ (2013). Managing the underlying cause of cystic fibrosis: a future role for potentiators and correctors. Paediatr Drugs 15: 393-402.
64. Galons H, Oumata N , Meijer L (2010). Cyclin-dependent kinase inhibitors: a survey of recent patent literature. Expert Opin Ther Pat 20: 377-404.
65. Ganapathi SB, Kester M, Elmslie KS (2009). State-dependent block of HE RG potassium channels by R-roscovitine: implications for cancer therapy. Am J Physiol Cell Physiol 296: C701-C710.
66. Gong Q, Jones MA, Zhou Z (2006). Mechanisms of pharmacological rescue of trafficking-defective hERG mutant channels in human long QT syndrome. J Biol Chem 281: 4069-4074.
67. Gray NS, Wodicka L, Thunnissen AM, Norman TC, Kwon S, Espinoza FH et al. (1998). Exploiting chemical libraries , structure, and genomics in the search for kinase inhibitors. Science 281: 533-538.
68. Herczenik E, Gebbink MF (2008). Molecular and cellular aspects of protein misfolding and disease. FASEB J 22: 2115-2133.
69. Hsieh WS, Soo R, Peh BK, Loh T, Dong D, Soh D et al. (2009). Pharmacodynamic effects of seliciclib, an orally administered cell cycle modulator, in undifferentiated nasopharyngeal cancer. C lin Cancer Res 15: 1435-1442.
70. Hutt DM, Herman D, Rodrigues AP, Noel S, Pilewski JM, Matteson J et al. (2010). Reduced histone deacetylase 7 activity restores function to misfolded CFTR in cystic fibrosis. Nat Chem Biol 6: 25-33.
71. Jefferson DM, Valentich JD, Marini FC, Grubman SA, Iannuzzi MC, Dorkin HL et al. (1990). Expression of normal and cystic fibrosis phenotypes by continuous airway epithelial cell lines. Am J Physiol 259 (6 Pt 1): 496-505.
72. Jensen TJ, Loo MA, Pind S, Williams DB, Goldberg AL, Riordan JR (1995). Multiple proteolytic systems, including the proteasome, contribute to CFTR processing. Cell 83: 12 9-135.
73. Johnson LG,Mewshaw JP,Ni H,Friedmann T,Boucher RC,Olsen JC 1998 Effect of host modification and age on airway epithelial gene transfer mediated by a murine leukemia virus-derived vector J Virol 72, 8861-8872.
74. Keller DI, Rougier JS, Kucera JP, Benammar N, Fressart V, Guicheney P et al. (2005). Brugada syndrome and fever: genetic and molecular characterization of patients carrying SCN 5A mutations. Cardiovasc Res 67: 510-519.
75. Knockaert M, Greengard P, Meijer L (2002). Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci 23: 417-425.
76. Li H, Findlay IA, Sheppard DN (2004). The relationship between cell proliferation, Cl-secretion, and renal cyst growth: a study using CFTR inhibitors. Kidney Int 66: 1926-1938.
77. Loo TW, Bartlett MC, Clarke DM (2004). Thapsigargin or curcumin does not promote maturation of processing mutants of the ABC transporters CFTR, and P-glycoprotein. Biochem Biophys Res Commun 325: 580-585.
78. Lubamba B, Lebacq J, Lebecque P, Vanbever R, Leonard A, Wallemacq P et al. (2009). Airway delivery of low-dose miglustat normalizes nasal potential difference in F508del cystic fibrosis mice. Am J Respir Crit Care Med 179: 1022-1028.
79. Lukacs GL, Verkman AS (2012). CFTR: folding, misfolding and correcting the DeltaF508 conformational defect. Trends Mol Med 18: 81-91.
80. Margolskee RF, McHendry-Rinde B, Horn R (1993). Panning transfected cells for electrophysiological studies. Biotechniques 15: 906-911.
81. Meijer L, Raymond E (2003). Roscovitine and other purines as kinase inhibitors. From starfish oocytes to clinical trials. Acc Chem Res 36: 417-425.
82. Meijer L, Borgne A, Mulner O, Chong JP, Blow JJ, Inagaki N et al. (1997). Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the c yclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem 243: 527-536.
83. Mercier A, Clément R, Harnois T, Bourmeyster N, Faivre JF, Findlay I et al. (2012). The ?1-subunit of Na(v)1.5 cardi ac sodium channel is required for a dominant negative effect through ? interaction. PLoS ONE 7: e48690.
84. Meusser B, Hirsch C, Jarosch E, Sommer T (2005). ERAD: the long road to destruction. Nat Cell Biol 7: 766-772.
85. Moriceau S, Kantari C, Mocek J, Davezac N, Gabillet J, Guerrer a IC et al. (2009). Coronin-1 is associated with neutrophil survival and is cleaved during apoptosis: potential implication in neutrophils from cystic fibrosis patients. J Immunol 182: 7254-7263.
86. Moriceau S, Lenoir G, Witko-Sarsat V (2010). In cystic fibrosis homozygotes and heterozygotes, neutrophil apoptosis is delayed and modulated by diamide or roscovitine: evidence for an innate neutrophil disturbance. J Innate Immun 2: 260-266.
87. Norez C, Antigny F, Becq F, Vandebrouck C (2006a ). Maintaining low Ca2+ level in the endoplasmic reticulum restores abnormal endogenous F508del-CFTR trafficking in airway epithelial cells. Traffic 7: 562-573.
88. Norez C, Noel S, Wilke M, Bijvelds M, Jorna H, Melin P et al. (2006b ). Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the alpha-glucosidase inhib itor miglustat. FEBS Lett 580: 2081-2086.
89. Norez C, Bilan F, Kitzis A, Mettey Y, Becq F (2008). Proteasome-dependent pharmacological rescue of cystic fibrosis transmembrane conductance regulator reve aled by mutation of glycine 622. J Pharmacol Exp Ther 325: 89-99.
90. Norez C, Antigny F, Noel S, Vandebrouck C, Becq F (2009). A cystic fibrosis respiratory epithelial cell chronically treated by miglu stat acquires a non-cystic fibrosis-like phenotype. Am J Respir Cell Mol Biol 41: 217-225.
91. BJP C Norez et al. 4848 British Journal of Pharmacology (2014) 171 4831-4849
92. Oumata N, Ferandin Y, Meijer L, Galo ns H (2009). Practical synthesis of roscovitine and CR8. Org Process Res Dev 13: 641-644.
93. Palmer AE, Tsien RY (2006). Measuring calcium signaling using genetically targetable fluorescent indicators. Nat Protoc 1: 1057-1065.
94. Pawson AJ, Sharman JL, Benson HE, Faccenda E, Alexander SP, Buneman OP et al.; NC-IUPHAR (2014). The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands. Nucl Acids Res 42 (Database Issue): D1098-D1106.
95. Pedemonte N,Diena T,Caci E,Nieddu E,Mazzei M,Ravazzolo R,et al. 2005 Antihypertensive 1,4-dihydropyridines as correctors of the cystic fibrosis transmembrane conductance regulator channel gating defect caused by cystic fibrosis mutations Mol Pharmacol 68 1736-1746.
96. Reinhardt J, Ferandin Y, Meijer L (2007). Purification of CK1 by affinity chromatography on immobilised axin. Protein Expr Purif 54: 101-109.
97. Riordan JR (2008). CFTR function and prospects for therapy. Annu Rev Biochem 77: 701-726.
98. Rossi AG, Saw atzky DA, Walker A, Ward C, Sheldrake TA, Riley NA et al. (2006). Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat Med 12: 1056-1064.
99. Rubenstein RC, Zeitlin PL (1998). A pilot clinical trial of oral sodium 4-phenylbutyrate (Buphenyl) in deltaF508-homozygous cystic fibrosis patients: partial restoration of nasal epithelial CFTR function. Am J Respir Crit Care Me d 157: 484-490.
100. Rubenstein RC, Zeitlin PL (2000). Sodium 4-phenylbutyrate downregulates Hsc70: implications for intracellular trafficking of DeltaF508-CFTR. Am J Physiol Cell Physiol 278: C259-C267.
101. Schultz BD, Frizzell RA, Bridges RJ (1999). Rescue of dysfunctional deltaF508-CFTR chloride channel activity by IBMX. J Membr Biol 170: 51-66.
102. Sheppard DN, Welsh MJ (1993). Inhibition of the cystic fibrosis transmembrane conductance regulator by ATP-sensitive K + channel regulators. Ann N Y Acad Sci 707: 275-284.
103. Tang L, Li MH, Cao P, Wang F, Chang WR, Bach S et al. (2 005). Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives. J Biol Chem 280: 31220-31229.
104. Tomizawa K, Ohta J, Matsushita M, Moriwaki A, Li ST, Takei K et al. (20 02). Cdk5/p35 regulates neurotransmitter release through phosphorylation and downregulation of P/Q-type voltage-dependent calcium channel activity. J Neurosci 22: 2590-2597.
105. Tsubuki S, Kawasaki H, Saito Y, Miyashita N, Inomata M, Kawashima S (1993). Purification and characterization of a Z-Leu-Leu-Leu-MCA degrading protease expected to regulate neurite formation: a novel catalytic activity in proteasome. Biochem Biophys Res Commun 196: 1195-1201.
106. Van GF, Straley KS, Cao D, González J, Hadida S, Hazlewood A et al. (2006). Rescue of DeltaF508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecu les. Am J Physiol Lung Cell Mol Physiol 290: L1117-L1130.
107. Van GF, Hadida S, Grootenhuis PD, Burton B, Stack JH, Straley KS et al. (2011). Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A 108: 18843-18848.
108. Vesely J, Havlicek L, Strnad M, Blow JJ, Donella-Deana A, Pinna L et al. (1994). Inhibition of cyclin-dep endent kinases by purine analogues. Eur J Biochem 224: 771-786.
109. Vij N, Fang S, Zeitlin PL (2006). Selective inhibition of endoplasmic reticulum-Associated degradation rescues DeltaF508-cystic fibrosis trans membrane regulator and suppresses interleukin-8 levels: therapeutic implications. J Biol Chem 281: 17369-17378.
110. Wang X, Venable J, LaPointe P, Hutt DM, Koulov AV, Coppinger J et al. (2006). Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell 127: 803-815.
111. Wang XF, Reddy MM, Quinton PM (2004). Effects of a new cystic fibrosis transmembrane conductance regulator inhibitor on Clconductance in human sweat ducts. Exp Physiol 89: 417-425.
112. Wang Y, Loo TW, Bartlett MC, Clarke DM (2007). Additive effect of multiple pharmacological chaperones on maturation of CFTR processing mutants. Biochem J 406: 257-263.
113. Ward CL, Omura S, Kopito RR (1995). Degradation of CFTR by the ubiquitin-proteasome pathway. Cell 83: 121-127.
114. Wesierska-Gadek J, Chamrad I, Krystof V (2009). Novel potent pharmacological cyclin-dependent kinase inhibitors. Future Med Chem 1: 1561-1581.
115. Yarotskyy V, Gao G, Du L, Ganapathi SB, Peterson BZ, Elmslie KS (2010). Roscovitine binds to novel L-channel (CaV1.2) sites that separately affect activation and inactivation. J Biol Chem 285: 43-53.
116. Yazawa M,Hsueh B,Jia X,Pasca AM,Bernstein JA,Hallmayer J,et al. 2011 Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome Nature 471, 230-234.
117. Yurko-Mauro KA, Reenstra WW (1998). Prostaglandin F2alpha stimulates CFTR activity by PKA-And PKC-dependent phosphorylation. Am J Physiol 275 (3 Pt 1): C653-C660.
118. Zaman K, McPherson M, Vaughan J, Hunt J, Mendes F, Gaston B et al. (2001). S-nitrosoglutathione increases cystic fibrosis transmembrane regulator maturation. Biochem Biophys Res Commun 284: 65-70.