Endoplasmic reticulum-targeted subunit toxins provide a new approach to rescue misfolded mutant proteins and revert cell models of genetic diseases

PLoS ONE

Volumn 11, Issue 12, 2016, Pages

  Adnan, Humaira ^a   Zhang, Zhenbo ^a   Park, Hyun Joo ^a   Tailor, Chetankumar ^b   Che, Clare ^a   Kamani, Mustafa ^a   Spitalny, George ^c   Binnington, Beth ^a   Lingwood, Clifford ^a,d  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

^b HOSPITAL FOR SICK CHILDREN RESEARCH INSTITUTE   (Canada)

^c ERAD Therapeutics   (Canada)

^d UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLERA TOXIN; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; GLUCOSYLCERAMIDASE; LEUCINE; MUTANT PROTEIN; VEROTOXIN 1; SHIGA TOXIN; TOXIN;

ALPHA CHAIN; AMINO TERMINAL SEQUENCE; ARTICLE; BRONCHIOLE EPITHELIUM; CELL MATURATION; CELL SURFACE; CHLORIDE TRANSPORT; CONTROLLED STUDY; CYSTIC FIBROSIS; CYTOPATHOLOGY; DISEASE MODEL; DRUG EFFICACY; DRUG MECHANISM; DRUG STRUCTURE; DRUG TARGETING; EMBRYO; ENDOPLASMIC RETICULUM ASSOCIATED DEGRADATION; ENZYME INDUCTION; FIBROBLAST; GAUCHER DISEASE; GENE INACTIVATION; GENETIC DISORDER; GOLGI COMPLEX; HUMAN; HUMAN CELL; PROTEIN EXPRESSION; PROTEIN MISFOLDING; STABLE TRANSFECTION; STRUCTURE ACTIVITY RELATION; TOXIN STRUCTURE; UPREGULATION; BIOLOGICAL MODEL; CHEMISTRY; CLASSIFICATION; DRUG EFFECTS; ENDOPLASMIC RETICULUM; FLUORESCENCE MICROSCOPY; GENETICS; HEK293 CELL LINE; METABOLISM; MUTATION; PROTEIN FOLDING; PROTEIN TRANSPORT; PROTEOSTASIS DEFICIENCIES; WESTERN BLOTTING;

BLOTTING, WESTERN; CHOLERA TOXIN; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; ENDOPLASMIC RETICULUM; ENDOPLASMIC RETICULUM-ASSOCIATED DEGRADATION; HEK293 CELLS; HUMANS; MICROSCOPY, FLUORESCENCE; MODELS, BIOLOGICAL; MUTATION; PROTEIN FOLDING; PROTEIN TRANSPORT; PROTEOSTASIS DEFICIENCIES; SHIGA TOXINS; TOXINS, BIOLOGICAL;

EID: 85006054953     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0166948     Document Type: Article

References (104)

1. Meusser B, Hirsch C, Jarosch E, Sommer T. ERAD: the long road to destruction. Nature cell biology. 2005; 7(8):766-72. doi: 10.1038/ncb0805-766 PMID: 16056268
2. Kruse KB, Brodsky JL, McCracken AA. Autophagy: an ER protein quality control process. Autophagy. 2006; 2(2):135-7. PMID: 16874086
3. Horimoto S, Ninagawa S, Okada T, Koba H, Sugimoto T, Kamiya Y, et al. The Unfolded Protein Response Transducer ATF6 Represents a Novel Transmembrane-type Endoplasmic Reticulum-associated Degradation Substrate Requiring Both Mannose Trimming and SEL1L Protein. J Biol Chem. 2013; 288(44):31517-27. Epub 2013/09/18. doi: 10.1074/jbc.M113.476010 PMID: 24043630
4. Chen Y, Bellamy WP, Seabra MC, Field MC, Ali BR. ER-associated protein degradation is a common mechanism underpinning numerous monogenic diseases including Robinow syndrome. Hum Mol Genet. 2005; 14(17):2559-69. doi: 10.1093/hmg/ddi259 PMID: 16049033
5. Tropak MB, Reid SP, Guiral M, Withers SG, Mahuran D. Pharmacological enhancement of beta-hexosaminidase activity in fibroblasts from adult Tay-Sachs and Sandhoff Patients. J Biol Chem. 2004; 279(14):13478-87. doi: 10.1074/jbc.M308523200 PMID: 14724290
6. Loo TW, Bartlett MC, Wang Y, Clarke DM. The chemical chaperone CFcor-325 repairs folding defects in the transmembrane domains of CFTR-processing mutants. Biochem J. 2006; 395(3):537-42. Epub 2006/01/19. doi: 10.1042/BJ20060013 PMID: 16417523
7. Fan J-Q. A counterintuitive approach to treat enzyme deficiencies: use of enzyme inhibitors for restoring mutant enzyme activity. Biol Chem 2008; 389:1-11. doi: 10.1515/BC.2008.009 PMID: 18095864
8. Bendikov-Bar I, Maor G, Filocamo M, Horowitz M. Ambroxol as a pharmacological chaperone for mutant glucocerebrosidase. Blood Cells Mol Dis. 2013; 50(2):141-5. Epub 2012/11/20. doi: 10.1016/j. bcmd.2012.10.007 PMID: 23158495
9. Wang F, Song W, Brancati G, Segatori L. Inhibition of endoplasmic reticulum-associated degradation rescues native folding in loss of function protein misfolding diseases. J Biol Chem. 2011; 286 (50):43454-64. Epub 2011/10/19. doi: 10.1074/jbc.M111.274332 PMID: 22006919
10. Wilke M, Bot A, Jorna H, Scholte BJ, de Jonge HR. Rescue of murine F508del CFTR activity in native intestine by low temperature and proteasome inhibitors. PLoS One. 2012; 7(12):e52070. Epub 2013/01/04. doi: 10.1371/journal.pone.0052070 PMID: 23284872
11. Vij N, Fang S, Zeitlin PL. Selective inhibition of endoplasmic reticulum-associated degradation rescues DeltaF508-cystic fibrosis transmembrane regulator and suppresses interleukin-8 levels: therapeutic implications. J Biol Chem. 2006; 281(25):17369-78. doi: 10.1074/jbc.M600509200 PMID: 16621797
12. Magadan JG, Perez-Victoria FJ, Sougrat R, Ye Y, Strebel K, Bonifacino JS. Multilayered mechanism of CD4 downregulation by HIV-1 Vpu involving distinct ER retention and ERAD targeting steps. PLoS Pathog. 2010; 6(4):e1000869. Epub 2010/05/06. doi: 10.1371/journal.ppat.1000869 PMID: 20442859
13. Olzmann JA, Kopito RR, Christianson JC. The mammalian endoplasmic reticulum-associated degradation system. Cold Spring Harbor perspectives in biology. 2013; 5(9). Epub 2012/12/13.
14. Scott DC, Schekman R. Role of Sec61p in the ER-associated degradation of short-lived transmembrane proteins. The Journal of cell biology. 2008; 181(7):1095-105. Epub 2008/06/25. doi: 10.1083/jcb.200804053 PMID: 18573918
15. Hebert DN, Bernasconi R, Molinari M. ERAD substrates: which way out? Semin Cell Dev Biol. 2010; 21(5):526-32. Epub 2009/12/23. doi: 10.1016/j.semcdb.2009.12.007 PMID: 20026414
16. Wang B, Heath-Engel H, Zhang D, Nguyen N, Thomas DY, Hanrahan JW, et al. BAP31 interacts with Sec61 translocons and promotes retrotranslocation of CFTRDeltaF508 via the derlin-1 complex. Cell. 2008; 133(6):1080-92. Epub 2008/06/17. doi: 10.1016/j.cell.2008.04.042 PMID: 18555783
17. Schafer A, Wolf DH. Sec61p is part of the endoplasmic reticulum-associated degradation machinery. Embo J. 2009; 28(19):2874-84. Epub 2009/08/22. doi: 10.1038/emboj.2009.231 PMID: 19696741
18. Kaiser ML, Romisch K. Proteasome 19S RP binding to the Sec61 channel plays a key role in ERAD. PLoS One. 2015; 10(2):e0117260. Epub 2015/02/07. doi: 10.1371/journal.pone.0117260 PMID: 25658429
19. Teter K, Allyn RL, Jobling MG, Holmes RK. Transfer of the cholera toxin A1 polypeptide from the endoplasmic reticulum to the cytosol is a rapid process facilitated by the endoplasmic reticulum-associated degradation pathway. Infect Immun. 2002; 70:6166-71. doi: 10.1128/IAI.70.11.6166-6171.2002 PMID: 12379694
20. Lord JM, Deeks E, Marsden CJ, Moore K, Pateman C, Smith DC, et al. Retrograde transport of toxins across the endoplasmic reticulum membrane. Biochemical Society transactions. 2003; 31(Pt 6):1260-2. PMID: 14641038
21. Cho JA, Chinnapen DJ, Aamar E, Te Welscher YM, Lencer WI, Massol R. Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins. Frontiers in cellular and infection microbiology. 2012; 2:51. Epub 2012/08/25. doi: 10.3389/fcimb.2012.00051 PMID: 22919642
22. Noakes KL, Teisserenc HT, Lord JM, Dunbar PR, Cerundolo V, Roberts LM. Exploiting retrograde transport of Shiga-like toxin 1 for the delivery of exogenous antigens into the MHC class I presentation pathway. FEBS letters. 1999; 453:95-9. PMID: 10403383
23. Smith DC, Lord JM, Roberts LM, Tartour E, Johannes L. 1st class ticket to class I: protein toxins as pathfinders for antigen presentation. Traffic. 2002; 3(10):697-704. PMID: 12230467
24. Hazes B, Read RJ. Accumulating evidence suggests that several AB-toxins subvert the endoplasmic reticulum-associated protein degradation pathway to enter target cells. Biochem. 1997; 36 (37):11051-4.
25. LaPointe P, Wei X, Gariepy J. A role for the protease-sensitive loop region of Shiga-like toxin 1 in the retrotranslocation of its A1 domain from the endoplasmic reticulum lumen. J Biol Chem. 2005; 280 (24):23310-8. doi: 10.1074/jbc.M414193200 PMID: 15817449
26. Johannes L, Romer W. Shiga toxins-from cell biology to biomedical applications. Nat Rev Microbiol. 2010; 8(2):105-16. Epub 2009/12/22. doi: 10.1038/nrmicro2279 PMID: 20023663
27. Mayor T. Navigating the ERAD interaction network. Nature cell biology. 2012; 14(1):46-7. Epub 2011/12/24.
28. Hansen GH, Dalskov SM, Rasmussen CR, Immerdal L, Niels-Christiansen LL, Danielsen EM. Cholera toxin entry into pig enterocytes occurs via a lipid raft- and clathrin-dependent mechanism. Biochemistry. 2005; 44(3):873-82. doi: 10.1021/bi047959+ PMID: 15654743
29. Chinnapen DJ, Chinnapen H, Saslowsky D, Lencer WI. Rafting with cholera toxin: endocytosis and trafficking from plasma membrane to ER. FEMS Microbiol Lett. 2007; 266(2):129-37. doi: 10.1111/j. 1574-6968.2006.00545.x PMID: 17156122
30. Sandvig K, Bergan J, Dyve AB, Skotland T, Torgersen ML. Endocytosis and retrograde transport of Shiga toxin. Toxicon. 2010; 56:1181-5. Epub 2009/12/03. doi: 10.1016/j.toxicon.2009.11.021 PMID: 19951719
31. Lea N, Lord JM, Roberts LM. Proteolytic cleavage of the A subunit is essential for maximal cytotoxicity of Escherichia coli O157:H7 Shiga-like toxin-1. Microbiology. 1999; 145 (Pt 5):999-1004.
32. Khan F, Proulx F, Lingwood CA. Detergent-resistant globotriaosyl ceramide may define verotoxin/glomeruli-restricted hemolytic uremic syndrome pathology. Kidney Int. 2009; 75(11):1209-16. Epub 2009/02/13. doi: 10.1038/ki.2009.7 PMID: 19212418
33. Lencer WI, Saslowsky D. Raft trafficking of AB5 subunit bacterial toxins. Biochim Biophys Acta. 2005; 1746(3):314-21. doi: 10.1016/j.bbamcr.2005.07.007 PMID: 16153723
34. Endo Y, Tsurugi K, Yutsudo T, Takeda Y, Ogasawara K, Igarashi K. Site of the action of a vero toxin (VT2) from Escherichia coli O157:H7 and a Shiga toxin on eukaryotic ribosomes. Eur J Biochem. 1988; 171:45-50. PMID: 3276522
35. Gill DM, Meren R. ADP-ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. Proc Natl Acad Sci U S A. 1978; 75(7):3050-4. Epub 1978/07/01. PMID: 210449
36. Kuroiwa T, Sakaguchi M, Mihara K, Omura T. Systematic analysis of stop-transfer sequence for microsomal membrane. J Biol Chem. 1991; 266(14):9251-5. PMID: 2026623
37. Hanrahan JW, Sampson HM, Thomas DY. Novel pharmacological strategies to treat cystic fibrosis. Trends Pharmacol Sci. 2013; 34(2):119-25. Epub 2013/02/06. doi: 10.1016/j.tips.2012.11.006 PMID: 23380248
38. Castilla J, Risquez R, Higaki K, Nanba E, Ohno K, Suzuki Y, et al. Conformationally-locked N-glycosides: Exploiting long-range non-glycone interactions in the design of pharmacological chaperones for Gaucher disease. Eur J Med Chem. 2015; 90:258-66. Epub 2014/12/03. doi: 10.1016/j.ejmech.2014. 11.002 PMID: 25461326
39. Wen SX, Teel LD, Judge NA, O'Brien AD. Genetic toxoids of Shiga toxin types 1 and 2 protect mice against homologous but not heterologous toxin challenge. Vaccine. 2006; 24(8):1142-8. doi: 10.1016/j.vaccine.2005.08.094 PMID: 16198455
40. Douce G, Fontana M, Pizza M, Rappuoli R, Dougan G. Intranasal immunogenicity and adjuvanticity of site-directed mutant derivatives of cholera toxin. Infection and immunity. 1997; 65(7):2821-8. Epub 1997/07/01. PMID: 9199455
41. Yasuda Y, Matano K, Asai T, Tochikubo K. Affinity purification of recombinant cholera toxin B subunit oligomer expressed in Bacillus brevis for potential human use as a mucosal adjuvant. FEMS Immunol Med Microbiol. 1998; 20(4):311-8. Epub 1998/06/17. PMID: 9626936
42. Trzcinska-Daneluti AM, Ly D, Huynh L, Jiang C, Fladd C, Rotin D. High-content functional screen to identify proteins that correct F508del-CFTR function. Molecular & cellular proteomics: MCP. 2009; 8 (4):780-90. Epub 2008/12/18.
43. Rowe SM, Pyle LC, Jurkevante A, Varga K, Collawn J, Sloane PA, et al. DeltaF508 CFTR processing correction and activity in polarized airway and non-airway cell monolayers. Pulm Pharmacol Ther. 2010; 23(4):268-78. Epub 2010/03/17. doi: 10.1016/j.pupt.2010.02.001 PMID: 20226262
44. Maegawa GH, Tropak MB, Buttner JD, Rigat BA, Fuller M, Pandit D, et al. Identification and characterization of ambroxol as an enzyme enhancement agent for Gaucher disease. J Biol Chem. 2009; 284 (35):23502-16. doi: 10.1074/jbc.M109.012393 PMID: 19578116
45. Baxter DF, Kirk M, Garcia AF, Raimondi A, Holmqvist MH, Flint KK, et al. A novel membrane potentialsensitive fluorescent dye improves cell-based assays for ion channels. Journal of biomolecular screening. 2002; 7(1):79-85. Epub 2002/03/19. doi: 10.1089/108705702753520369 PMID: 11897058
46. Maitra R, Sivashanmugam P, Warner K. A rapid membrane potential assay to monitor CFTR function and inhibition. Journal of biomolecular screening. 2013; 18(9):1132-7. Epub 2013/05/09. doi: 10.1177/1087057113488420 PMID: 23653393
47. Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989; 245 (4922):1066-73. PMID: 2475911
48. Khine AA, Tam P, Nutikka A, Lingwood CA. Brefeldin A and filipin distinguish two Globotriaosyl ceramide/Verotoxin-1 intracellular trafficking pathways involved in Vero cell cytotoxicity. Glycobiology. 2004; 14:701-12. doi: 10.1093/glycob/cwh085 PMID: 15102715
49. Wang X, Koulov AV, Kellner WA, Riordan JR, Balch WE. Chemical and biological folding contribute to temperature-sensitive DeltaF508 CFTR trafficking. Traffic. 2008; 9(11):1878-93. Epub 2008/09/04. doi: 10.1111/j.1600-0854.2008.00806.x PMID: 18764821
50. Farinha CM, Amaral MD. Most F508del-CFTR is targeted to degradation at an early folding checkpoint and independently of calnexin. Mol Cell Biol. 2005; 25(12):5242-52. doi: 10.1128/MCB.25.12.5242-5252.2005 PMID: 15923638
51. Varga K, Goldstein RF, Jurkuvenaite A, Chen L, Matalon S, Sorscher EJ, et al. Enhanced cell-surface stability of rescued DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) by pharmacological chaperones. Biochem J. 2008; 410(3):555-64. doi: 10.1042/BJ20071420 PMID: 18052931
52. Van Goor F, Hadida S, Grootenhuis PD, Burton B, Stack JH, Straley KS, et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A. 2011; 108(46):18843-8. Epub 2011/10/07. doi: 10.1073/pnas.1105787108 PMID: 21976485
53. Veit G, Avramescu RG, Perdomo D, Phuan PW, Bagdany M, Apaja PM, et al. Some gating potentiators, including VX-770, diminish DeltaF508-CFTR functional expression. Sci Transl Med. 2014; 6 (246):246ra97. Epub 2014/08/08. doi: 10.1126/scitranslmed.3008889 PMID: 25101887
54. Cholon DM, Quinney NL, Fulcher ML, Esther CR Jr., Das J, Dokholyan NV, et al. Potentiator ivacaftor abrogates pharmacological correction of DeltaF508 CFTR in cystic fibrosis. Sci Transl Med. 2014; 6 (246):246ra96. Epub 2014/08/08. doi: 10.1126/scitranslmed.3008680 PMID: 25101886
55. Thompson HW, Mera R, Prasad C. A Description of the Appropriate Use of Student's t-Test. Nutritional neuroscience. 1998; 1(2):165-72. Epub 1998/01/01. doi: 10.1080/1028415X.1998.11747226 PMID: 27406022
56. Shun Z, Silverberg A, Chang CK, Ouyang P. Dunnett's many-to-one test and least square means. Journal of biopharmaceutical statistics. 2003; 13(1):17-28. Epub 2003/03/15. doi: 10.1081/BIP-120017723 PMID: 12635900
57. Sawkar AR, D'Haeze W, Kelly JW. Therapeutic strategies to ameliorate lysosomal storage disorders-a focus on Gaucher disease. Cell Mol Life Sci. 2006; 63(10):1179-92. Epub 2006/03/29. doi: 10.1007/s00018-005-5437-0 PMID: 16568247
58. Sawkar AR, Schmitz M, Zimmer KP, Reczek D, Edmunds T, Balch WE, et al. Chemical chaperones and permissive temperatures alter localization of Gaucher disease associated glucocerebrosidase variants. ACS chemical biology. 2006; 1(4):235-51. doi: 10.1021/cb600187q PMID: 17163678
59. Liang G, Li Q, Tang Y, Kokame K, Kikuchi T, Wu G, et al. Polycystin-2 is regulated by endoplasmic reticulum-associated degradation. Hum Mol Genet. 2008; 17(8):1109-19. Epub 2008/01/08. doi: 10.1093/hmg/ddm383 PMID: 18178578
60. Wang L, Dong H, Soroka CJ, Wei N, Boyer JL, Hochstrasser M. Degradation of the bile salt export pump at endoplasmic reticulum in progressive familial intrahepatic cholestasis type II. Hepatology. 2008; 48(5):1558-69. doi: 10.1002/hep.22499 PMID: 18798335
61. Yagishita N, Yamasaki S, Nishioka K, Nakajima T. Synoviolin, protein folding and the maintenance of joint homeostasis. Nature clinical practice Rheumatology. 2008; 4(2):91-7. Epub 2008/02/01. doi: 10.1038/ncprheum0699 PMID: 18235538
62. Kang JQ, Shen W, Macdonald RL. Two molecular pathways (NMD and ERAD) contribute to a genetic epilepsy associated with the GABA(A) receptor GABRA1 PTC mutation, 975delC, S326fs328X. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2009; 29(9):2833-44.
63. Gao H, Wang Y, Wegierski T, Skouloudaki K, Putz M, Fu X, et al. PRKCSH/80K-H, the protein mutated in polycystic liver disease, protects polycystin-2/TRPP2 against HERP-mediated degradation. Hum Mol Genet. 2010; 19(1):16-24. Epub 2009/10/06. doi: 10.1093/hmg/ddp463 PMID: 19801576
64. Murphy LA, Ramirez EA, Trinh VT, Herman AM, Anderson VC, Brewster JL. Endoplasmic reticulum stress or mutation of an EF-hand Ca(2+)-binding domain directs the FKBP65 rotamase to an ERADbased proteolysis. Cell stress & chaperones. 2011; 16(6):607-19. Epub 2011/07/16.
65. Ugolino J, Fang S, Kubisch C, Monteiro MJ. Mutant Atp13a2 proteins involved in parkinsonism are degraded by ER-associated degradation and sensitize cells to ER-stress induced cell death. Hum Mol Genet. 2011; 20(18):3565-77. Epub 2011/06/15. doi: 10.1093/hmg/ddr274 PMID: 21665991
66. Bhargava A, Voronov I, Wang Y, Glogauer M, Kartner N, Manolson MF. Osteopetrosis mutation R444L causes ER retention and misprocessing of vacuolar H+-ATPase a3 subunit. J Biol Chem. 2012. Epub 2012/06/12.
67. Chiang WC, Kroeger H, Sakami S, Messah C, Yasumura D, Matthes MT, et al. Robust Endoplasmic Reticulum-Associated Degradation of Rhodopsin Precedes Retinal Degeneration. Mol Neurobiol. 2014. Epub 2014/10/02.
68. Wang YJ, Tayo BO, Bandyopadhyay A, Wang H, Feng T, Franceschini N, et al. The association of the vanin-1 N131S variant with blood pressure is mediated by endoplasmic reticulum-associated degradation and loss of function. PLoS Genet. 2014; 10(9):e1004641. Epub 2014/09/19. doi: 10.1371/journal. pgen.1004641 PMID: 25233454
69. Wang Q, Shinkre BA, Lee JG, Weniger MA, Liu Y, Chen W, et al. The ERAD inhibitor Eeyarestatin I is a bifunctional compound with a membrane-binding domain and a p97/VCP inhibitory group. PLoS One. 2010; 5(11):e15479. Epub 2010/12/03. doi: 10.1371/journal.pone.0015479 PMID: 21124757
70. Shirley RB, Kaddour-Djebbar I, Patel DM, Lakshmikanthan V, Lewis RW, Kumar MV. Combination of proteasomal inhibitors lactacystin and MG132 induced synergistic apoptosis in prostate cancer cells. Neoplasia. 2005; 7(12):1104-11. Epub 2005/12/16. PMID: 16354593
71. Wu KL, van Wieringen W, Vellenga E, Zweegman S, Lokhorst HM, Sonneveld P. Analysis of the efficacy and toxicity of bortezomib for treatment of relapsed or refractory multiple myeloma in community practice. Haematologica. 2005; 90(7):996-7. Epub 2005/07/06. PMID: 15996946
72. Einsele H. Bortezomib. Recent Results Cancer Res. 2010; 184:173-87. Epub 2010/01/15. doi: 10.1007/978-3-642-01222-8-12 PMID: 20072838
73. Kincaid MM, Cooper AA. ERADicate ER stress or die trying. Antioxid Redox Signal. 2007; 9 (12):2373-87. doi: 10.1089/ars.2007.1817 PMID: 17883326
74. McKibbin C, Mares A, Piacenti M, Williams H, Roboti P, Puumalainen M, et al. Inhibition of protein translocation at the endoplasmic reticulum promotes activation of the unfolded protein response. Biochem J. 2012; 442(3):639-48. Epub 2011/12/08. doi: 10.1042/BJ20111220 PMID: 22145777
75. Merksamer PI, Papa FR. The UPR and cell fate at a glance. J Cell Sci. 2010; 123(Pt 7):1003-6. Epub 2010/03/25. doi: 10.1242/jcs.035832 PMID: 20332117
76. Tsai YC, Weissman AM. The Unfolded Protein Response, Degradation from Endoplasmic Reticulum and Cancer. Genes Cancer. 2010; 1(7):764-78. Epub 2011/02/19. doi: 10.1177/1947601910383011 PMID: 21331300
77. Brem GJ, Mylonas I, Bruning A. Eeyarestatin causes cervical cancer cell sensitization to bortezomib treatment by augmenting ER stress and CHOP expression. Gynecol Oncol. 2013; 128(2):383-90. Epub 2012/10/31. doi: 10.1016/j.ygyno.2012.10.021 PMID: 23107612
78. Guerriero CJ, Brodsky JL. The delicate balance between secreted protein folding and endoplasmic reticulum-associated degradation in human physiology. Physiological reviews. 2012; 92(2):537-76. Epub 2012/04/27. doi: 10.1152/physrev.00027.2011 PMID: 22535891
79. Elfrink HL, Zwart R, Baas F, Scheper W. Inhibition of endoplasmic reticulum associated degradation reduces endoplasmic reticulum stress and alters lysosomal morphology and distribution. Mol Cells. 2013; 35(4):291-7. Epub 2013/03/22. doi: 10.1007/s10059-013-2286-9 PMID: 23515578
80. Majoul I, Schmidt T, Pomasanova M, Boutkevich E, Kozlov Y, Soling HD. Differential expression of receptors for Shiga and Cholera toxin is regulated by the cell cycle. J Cell Sci. 2002; 115(Pt 4):817-26. PMID: 11865037
81. Devenica D, Cikes Culic V, Vuica A, Markotic A. Biochemical, pathological and oncological relevance of Gb3Cer receptor. Med Oncol. 2011; 28 Suppl 1:S675-84. Epub 2010/11/12.
82. Muthing J, Schweppe CH, Karch H, Friedrich AW. Shiga toxins, glycosphingolipid diversity, and endothelial cell injury. Thrombosis and haemostasis. 2009; 101(2):252-64. PMID: 19190807
83. Chinnapen DJ, Hsieh WT, te Welscher YM, Saslowsky DE, Kaoutzani L, Brandsma E, et al. Lipid sorting by ceramide structure from plasma membrane to ER for the cholera toxin receptor ganglioside GM1. Developmental cell. 2012; 23(3):573-86. Epub 2012/09/15. doi: 10.1016/j.devcel.2012.08.002 PMID: 22975326
84. Falguieres T, Mallard F, Baron C, Hanau D, Lingwood C, Goud B, et al. Targeting of Shiga toxin b-subunit to retrograde transport route in association with detergent-resistant membranes. Mol Biol Cell. 2001; 12(8):2453-68. PMID: 11514628
85. Fujinaga Y, Wolf AA, Rodighiero C, Wheeler H, Tsai B, Allen L, et al. Gangliosides that associate with lipid rafts mediate transport of cholera and related toxins from the plasma membrane to ER. Mol Biol Cell. 2003; 14(12):4783-93. doi: 10.1091/mbc.E03-06-0354 PMID: 13679513
86. Wolf AA, Jobling MG, Saslowsky DE, Kern E, Drake KR, Kenworthy AK, et al. Attenuated endocytosis and toxicity of a mutant cholera toxin with decreased ability to cluster ganglioside GM1 molecules. Infection and immunity. 2008; 76(4):1476-84. doi: 10.1128/IAI.01286-07 PMID: 18212085
87. Dixit G, Mikoryak C, Hayslett T, Bhat A, Draper RK. Cholera toxin up-regulates endoplasmic reticulum proteins that correlate with sensitivity to the toxin. Exp Biol Med (Maywood). 2008; 233(2):163-75.
88. Garcia-Castillo MD, Tran T, Bobard A, Renard HF, Rathjen SJ, Dransart E, et al. Retrograde transport is not required for cytosolic translocation of Shiga toxin B-subunit. J Cell Sci. 2015. Epub 2015/05/16.
89. Tam P, Mahfoud R, Nutikka A, Khine A, Binnington B, Paroutis P, et al. Differential Intracellular Trafficking and Binding of Verotoxin 1 and Verotoxin 2 to Globotriaosylceramide-containing Lipid Assemblies. J Cell Physiol. 2008; 216:750-63. doi: 10.1002/jcp.21456 PMID: 18446787
90. Amessou M, Carrez D, Patin D, Sarr M, Grierson DS, Croisy A, et al. Retrograde delivery of photosensitizer (TPPp-O-beta-GluOH)3 selectively potentiates its photodynamic activity. Bioconjug Chem. 2008; 19(2):532-8. doi: 10.1021/bc7003999 PMID: 18205329
91. Arab S, Rutka J, Lingwood C. Verotoxin induces apoptosis and the complete, rapid, long-term elimination of human astrocytoma xenografts in nude mice. Oncol Res. 1999; 11:33-9. PMID: 10451029
92. Ishitoya S, Kurazono H, Nishiyama H, Nakamura E, Kamoto T, Habuchi T, et al. Verotoxin induces rapid elimination of human renal tumor xenografts in SCID mice. J Urol. 2004; 171(3):1309-13. doi: 10.1097/01.ju.0000100110.11129.85 PMID: 14767339
93. Wesche J, Rapak A, Olsnes S. Dependence of ricin toxicity on translocation of the toxin A-chain from the endoplasmic reticulum to the cytosol. J Biol Chem. 1999; 274:34443-9. PMID: 10567425
94. Schmitz A, Herrgen H, Winkeler A, Herzog V. Cholera toxin is exported from microsomes by the Sec61p complex. The Journal of cell biology. 2000; 148(6):1203-12. PMID: 10725333
95. Yu M, Haslam DB. Shiga toxin is transported from the endoplasmic reticulum following interaction with the luminal chaperone HEDJ/ERdj3. Infection and immunity. 2005; 73(4):2524-32. doi: 10.1128/IAI. 73.4.2524-2532.2005 PMID: 15784599
96. Moreau D, Kumar P, Wang SC, Chaumet A, Chew SY, Chevalley H, et al. Genome-wide RNAi screens identify genes required for Ricin and PE intoxications. Developmental cell. 2011; 21(2):231-44. Epub 2011/07/26. doi: 10.1016/j.devcel.2011.06.014 PMID: 21782526
97. Dang H, Klokk TI, Schaheen B, McLaughlin BM, Thomas AJ, Durns TA, et al. Derlin-dependent retrograde transport from endosomes to the Golgi apparatus. Traffic. 2011; 12(10):1417-31. Epub 2011/07/05. doi: 10.1111/j.1600-0854.2011.01243.x PMID: 21722281
98. Eshraghi A, Dixon SD, Tamilselvam B, Kim EJ, Gargi A, Kulik JC, et al. Cytolethal distending toxins require components of the ER-associated degradation pathway for host cell entry. PLoS Pathog. 2014; 10(7):e1004295. Epub 2014/08/01. doi: 10.1371/journal.ppat.1004295 PMID: 25078082
99. Bernardi KM, Forster ML, Lencer WI, Tsai B. Derlin-1 facilitates the retro-translocation of cholera toxin. Mol Biol Cell. 2008; 19(3):877-84. Epub 2007/12/21. doi: 10.1091/mbc.E07-08-0755 PMID: 18094046
100. Rabeh WM, Bossard F, Xu H, Okiyoneda T, Bagdany M, Mulvihill CM, et al. Correction of both NBD1 energetics and domain interface is required to restore DeltaF508 CFTR folding and function. Cell. 2012; 148(1-2):150-63. Epub 2012/01/24. doi: 10.1016/j.cell.2011.11.024 PMID: 22265408
101. Okiyoneda T, Veit G, Dekkers JF, Bagdany M, Soya N, Xu H, et al. Mechanism-based corrector combination restores DeltaF508-CFTR folding and function. Nat Chem Biol. 2013; 9(7):444-54. Epub 2013/05/15. doi: 10.1038/nchembio.1253 PMID: 23666117
102. Okiyoneda T, Barriere H, Bagdany M, Rabeh WM, Du K, Hohfeld J, et al. Peripheral protein quality control removes unfolded CFTR from the plasma membrane. Science. 2010; 329(5993):805-10. Epub 2010/07/03. doi: 10.1126/science.1191542 PMID: 20595578
103. Van Goor F, Hadida S, Grootenhuis PD, Burton B, Cao D, Neuberger T, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A. 2009; 106 (44):18825-30. Epub 2009/10/23. doi: 10.1073/pnas.0904709106 PMID: 19846789
104. McHugh ML. Multiple comparison analysis testing in ANOVA. Biochemia medica. 2011; 21(3):203-9. Epub 2011/01/01. PMID: 22420233