DOI QR코드

DOI QR Code

Emerging roles of protein disulfide isomerase in cancer

  • Lee, Eunyoug (Department of Bio and Environmental Technology, Seoul Women's University) ;
  • Lee, Do Hee (Department of Bio and Environmental Technology, Seoul Women's University)
  • Received : 2017.06.05
  • Published : 2017.08.31

Abstract

The protein disulfide isomerase (PDI) family is a group of multifunctional endoplasmic reticulum (ER) enzymes that mediate the formation of disulfide bonds, catalyze the cysteine-based redox reactions and assist the quality control of client proteins. Recent structural and functional studies have demonstrated that PDI members not only play an essential role in the proteostasis in the ER but also exert diverse effects in numerous human disorders including cancer and neurodegenerative diseases. Increasing evidence suggests that PDI is actively involved in the proliferation, survival, and metastasis of several types of cancer cells. Although the molecular mechanism by which PDI contributes to tumorigenesis and metastasis remains to be understood, PDI is now emerging as a new therapeutic target for cancer treatment. In fact, several attempts have been made to develop PDI inhibitors as anti-cancer drugs. In this review, we discuss the properties and diverse functions of human PDI proteins and focus on recent findings regarding their roles in the state of diseases including cancer and neurodegeneration.

Keywords

References

  1. Galligan JJ and Petersen DR (2012) The human protein disulfide isomerase gene family. Hum Genomics 6, 6 https://doi.org/10.1186/1479-7364-6-6
  2. Bosnjak I, Bojovic V, Segvic-Bubic T et al (2014) Occurrence of protein disulfide bonds in different domains of life: a comparison of proteins from the Protein Data Bank. Prot Eng Des Selec 27, 65-72 https://doi.org/10.1093/protein/gzt063
  3. Depuydt M, Messens J and Collet JF (2011) How proteins form disulfide bonds. Antioxid Redox Signal 15, 49-66 https://doi.org/10.1089/ars.2010.3575
  4. Riemer J, Bulleid N and Herrmann JM (2009) Disulfide formation in the ER and mitochondria: Two solutions to a common process. Science 324, 1284-1287 https://doi.org/10.1126/science.1170653
  5. Ferrari DM and Soling HD (1999) The protein disulphideisomerase family: unravelling a string of folds. Biochem J 339, 1-10 https://doi.org/10.1042/bj3390001
  6. Hudson DA, Gannon SA and Thorpe C (2015) Oxidative protein folding: From thiol-disulfide exchange reactions to the redox poise of the endoplasmic reticulum. Free Radic Biol Med 80, 171-182 https://doi.org/10.1016/j.freeradbiomed.2014.07.037
  7. Hatahet F and Ruddock LW (2009) Protein disulfide isomerase: A critical evaluation of Its function in disulfide bond formation. Antoxid Redox Signal 11, 2807-2850 https://doi.org/10.1089/ars.2009.2466
  8. Wang L, Wang X and Wang CC (2015) Protein disulfide-isomerase, a folding catalyst and a redox-regulated chaperone. Free Radic Biol Med 83, 305-313 https://doi.org/10.1016/j.freeradbiomed.2015.02.007
  9. Yoshioka J (2015) Thioredoxin superfamily and its effects on cardiac physiology and pathology. Compr Physiol 5, 513-530
  10. Myllyharju J (2003) Prolyl 4-hydroxylases, the key enzymes of collagen biosynthesis. Matrix Biol 22, 15-24 https://doi.org/10.1016/S0945-053X(03)00006-4
  11. Soares Moretti AI and Martins Laurindo FR (2017) Protein disulfide isomerases: Redox connections in and out of the endoplasmic reticulum. Arch Biochem Biophys 617, 106-119 https://doi.org/10.1016/j.abb.2016.11.007
  12. Alanen HI, Williamson RA, Howard MJ et al (2003) Functional characterization of ERp18, a new endoplasmic reticulum-located thioredoxin superfamily member. J Biol Chem 278, 28912-28920 https://doi.org/10.1074/jbc.M304598200
  13. Kozlov G, Maattanen P, Thomas DY et al (2010) A structural overview of the PDI family of proteins. FEBS J 277, 3924-3936 https://doi.org/10.1111/j.1742-4658.2010.07793.x
  14. Appenzeller-Herzog C and Ellgaard L (2008) The human PDI family: Versatility packed into a single fold. Biochim Biophys Acta 1783, 535-548 https://doi.org/10.1016/j.bbamcr.2007.11.010
  15. Park SW, Zhen G, Verhaeghe C et al (2009) The protein disulfide isomerase AGR2 is essential for production of intestinal mucus. Proc Natl Acad Sci U S A 106, 6950-6955 https://doi.org/10.1073/pnas.0808722106
  16. Alanen HI, Williamson RA, Howard MJ et al (2006) ERp27, a new non-catalytic endoplasmic reticulum-located human protein disulfide isomerase family member Interacts with ERp57. J Biol Chem 281, 33727-33738 https://doi.org/10.1074/jbc.M604314200
  17. Ferrari DM, Nguyen Van P, Kratzin HD et al (1998) ERp28, a human endoplasmic-reticulum-lumenal protein, is a member of the protein disulfide isomerase family but lacks a CXXC thioredoxin-box motif. Eur J Biochem 255, 570-579 https://doi.org/10.1046/j.1432-1327.1998.2550570.x
  18. Novak P and Soukup T (2011) Calsequestrin distribution, structure and function, its role in normal and pathological situations and the effect of thyroid hormones. Physiol Res 60, 439-452
  19. Shin DW, Ma J and Kim DH (2003) The asp-rich region at the carboxyl-terminus of calsequestrin binds to $Ca^{2+}$ and interacts with triadin. FEBS Lett 486, 178-182
  20. Persson S, Rosenquist M, Knoblach B et al (2005) Diversity of the protein disulfide isomerase family: identification of breast tumor induced Hag2 and Hag3 as novel members of the protein family. Mol Phylogenet Evol 36, 734-740 https://doi.org/10.1016/j.ympev.2005.04.002
  21. Xu S, Sankar S and Neamati N (2014) Protein disulfide isomerase: a promising target for cancer therapy. Drug Discov Today 19, 1359-6446
  22. Brychtova V, Vojtesek B and Hrstka R (2011) Anterior gradient 2: a novel player in tumor cell biology. Cancer Lett 304, 1-7 https://doi.org/10.1016/j.canlet.2010.12.023
  23. Salmans ML, Zhao F and Andersen B (2013) The estrogen-regulated anterior gradient 2 (AGR2) protein in breast cancer: a potential drug target and biomarker. Breast Cancer Res 15, 204 https://doi.org/10.1186/bcr3408
  24. Gray TA, MacLaine NJ, Michie CO et al (2012) Anterior Gradient-3: a novel biomarker for ovarian cancer that mediates cisplatin resistance in xenograft models. J Immunol Methods 378, 20-32 https://doi.org/10.1016/j.jim.2012.01.013
  25. Hatahet F and Ruddock LW (2007) Substrate recognition by the protein disulfide isomerases. FEBS J 274, 5223-5234 https://doi.org/10.1111/j.1742-4658.2007.06058.x
  26. Winter J, Klappa P, Freedman RB et al (2002) Catalytic activity and chaperone function of human proteindisulfide isomerase are required for the efficient refolding of proinsulin. J Biol Chem 277, 310-317 https://doi.org/10.1074/jbc.M107832200
  27. Schultz-Norton JR, McDonald WH, Yates JR et al (2006) Protein disulfide isomerase serves as a molecular chaperone to maintain estrogen receptor ${\alpha}$ structure and function. Mol Endocrinol 20, 1982-1995 https://doi.org/10.1210/me.2006-0006
  28. Janiszewski M, Lopes LR, Carmo AO et al (2005) Regulation of NAD(P)H oxidase by associated protein disulfide isomerase in vascular smooth muscle cells. J Biol Chem 280, 40813-40819 https://doi.org/10.1074/jbc.M509255200
  29. Pescatore LA, Bonatto D, Forti FL et al (2012) Protein Disulfide Isomerase Is Required for Platelet-derived Growth Factor-induced Vascular Smooth Muscle Cell Migration, Nox1 NADPH Oxidase Expression, and RhoGTPase Activation. J Biol Chem 287, 29290-29300 https://doi.org/10.1074/jbc.M112.394551
  30. Jessop CE, Watkins RH, Simmons JJ et al (2009) Protein disulphide isomerase family members show distinct substrate specificity: P5 is targeted to BiP client proteins. J Cell Sci 122, 4287-4295 https://doi.org/10.1242/jcs.059154
  31. Maattanen P, Gehring K, Bergeron JJ et al (2010) Protein quality control in the ER: the recognition of misfolded proteins. Semin Cell Dev Biol 21, 500-511 https://doi.org/10.1016/j.semcdb.2010.03.006
  32. Ruddock LW, Freedman RB and Klappa P (2000) Specificity in substrate binding by protein folding catalysts: Tyrosine and tryptophan residues are the recognition motifs for the binding of peptides to the pancreas-specific protein disulfide isomerase PDIp. Protein Sci 9, 758-764
  33. Fu XM and Zhu BT (2010) Human pancreas-specific protein disulfide-isomerase (PDIp) can function as a chaperone independently of its enzymatic activity by forming stable complexes with denatured substrate proteins. Biochem J 429, 157-169 https://doi.org/10.1042/BJ20091954
  34. Dong GI, Wearsch PA, Peaper DR et al (2009) Insights into MHC Class I peptide loading from the structure of the Tapasin-ERp57 thiol oxidoreductase heterodimer. Immunity 30, 21-32 https://doi.org/10.1016/j.immuni.2008.10.018
  35. Peaper DR and Cressewell P (2008) The redox activity of ERp57 is not essential for its functions in MHC class I peptide loading. Proc Natl Acad Sci U S A 105, 10477-10482 https://doi.org/10.1073/pnas.0805044105
  36. Frenkel Z, Shenkman M, Kondratyev M et al (2004) Separate roles and different routing of Calnexin and ERp57 in endoplasmic reticulum quality control revealed by interactions with asialoglycoprotein receptor chains. Mol Biol Cell 15, 2133-2142 https://doi.org/10.1091/mbc.E03-12-0899
  37. Watts JC, Huo H, Bai Y et al (2009) Interactome analyses identify ties of PrP and its mammalian paralogs to oligomannosidic N-glycans and endoplasmic reticulumderived chaperones. PLoS Pathog 5, e1000608 https://doi.org/10.1371/journal.ppat.1000608
  38. Torres M, Medinas DB, Matamala JM et al (2015) The Protein-disulfide Isomerase ERp57 Regulates the Steady-state Levels of the Prion Protein. J Biol Chem 290, 23631-23645 https://doi.org/10.1074/jbc.M114.635565
  39. Molinari M, Galli C, Piccaluga et al (2002) V Sequential assistance of molecular chaperones and transient formation of covalent complexes during protein degradation from the ER. J Cell Biol 158, 247-257 https://doi.org/10.1083/jcb.200204122
  40. Lee SO, Cho KM, Cho SL et al (2010) Protein disulphide isomerase is required for signal peptide peptidasemediated protein degradation. EMBO J 29, 363-375 https://doi.org/10.1038/emboj.2009.359
  41. Meunier L, Usherwood YK, Chung KT et al (2002) A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins. Mol Biol Cell 13, 4456-4469 https://doi.org/10.1091/mbc.E02-05-0311
  42. Vinaik R, Kozlov G and Gehring K (2013) Structure of the non-catalytic domain of the protein disulfide isomeraserelated protein (PDIR) reveals function in protein binding. PLoS One 8, e62021 https://doi.org/10.1371/journal.pone.0062021
  43. Rutkevich LA, Cohen-Doyle MF, Brockmeier U et al (2010) Functional relationship between protein disulfide isomerase family members during the oxidative folding of human secretory proteins. Mol Biol Cell 21, 3093-3105 https://doi.org/10.1091/mbc.E10-04-0356
  44. Gorasia DG, Dudek NL, Safavi-Hemami H et al (2016) A prominent role of PDIA6 in processing of misfolded proinsulin. Biochim Biophys Acta 1864, 715-723 https://doi.org/10.1016/j.bbapap.2016.03.002
  45. van Lith M, Hartigan N, Hatch J et al (2005) PDILT, a divergent testis-specific protein disulfide isomerase with a non-classical SXXC motif that engages in disulfidedependent interactions in the endoplasmic reticulum. J Biol Chem 280, 1376-1383 https://doi.org/10.1074/jbc.M408651200
  46. Tokuhiro K, Ikawa M, Benham AM et al (2012) Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male fertility. Proc Natl Acad Sci U S A 109, 3850-3855 https://doi.org/10.1073/pnas.1117963109
  47. Anelli T, Stefania Ceppi S, Bergamelli L et al (2007) Sequential steps and checkpoints in the early exocytic compartment during secretory IgM biogenesis. EMBO J 26, 4177-4188 https://doi.org/10.1038/sj.emboj.7601844
  48. Hampe L, Radjainia M, Xu C et al (2015) Regulation and quality control of adiponectin assembly by endoplasmic reticulum chaperone ERp44. J Biol Chem 290, 18111-18123 https://doi.org/10.1074/jbc.M115.663088
  49. Vavassori S, Cortini M, Masui S et al (2013) A pH-regulated quality control cycle for surveillance of secretory protein assembly. Mol Cell 50, 783-792 https://doi.org/10.1016/j.molcel.2013.04.016
  50. Anelli T, Sannino S and Sitia R (2015) Proteostasis and "redoxtasis" in the secretory pathway: Tales of tails from ERp44 and immunoglobulins. Free Radic Biol Med 83, 323-330 https://doi.org/10.1016/j.freeradbiomed.2015.02.020
  51. Sullivan DC, Huminiecki L, Moore JW et al (2003) EndoPDI, a novel protein-disulfide isomerase-like protein that is preferentially expressed in endothelial cells acts as a stress survival factor. J Biol Chem 278, 47079-47088 https://doi.org/10.1074/jbc.M308124200
  52. Okumura M, Kadokura H and Inaba K (2015) Structures and functions of protein disulfide isomerase family members involved in proteostasis in the endoplasmic reticulum. Free Radic Biol Med 83, 314-322 https://doi.org/10.1016/j.freeradbiomed.2015.02.010
  53. Ushioda R, Hoseki J, Araki K et al (2008) ERdj5 is required as a disulfide reductase for degradation of misfolded proteins in the ER. Science 321, 569-572 https://doi.org/10.1126/science.1159293
  54. Oka OB, Pringle MA, Schopp IM et al (2013) ERdj5 is the ER reductase that catalyzes the removal of non-native disulfides and correct folding of the LDL receptor. Mol Cell 50, 793-804 https://doi.org/10.1016/j.molcel.2013.05.014
  55. Perri ER, Thomas CJ, Parakh S et al (2016) The Unfolded Protein Response and the Role of Protein Disulfide Isomerase in Neurodegeneration. Front Cell Dev Biol 3, 80
  56. Skovronsky DM, Lee VM and Trojanowski JQ (2006) Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications. Annu Rev Pathol 1, 151-170 https://doi.org/10.1146/annurev.pathol.1.110304.100113
  57. Parakh S and Atkin JD (2015) Novel roles for protein disulphide isomerase in disease states: a double edged sword? Front Cell Dev Biol 3, 1-11
  58. Wang SB, Shi Q, Xu Y et al (2012) Protein Disulfide Isomerase Regulates Endoplasmic Reticulum Stress and the Apoptotic Process during Prion Infection and PrP Mutant-Induced Cytotoxicity. PLoS One 7, 1-12
  59. Xu LR, Liu XL, Chen J et al (2013) Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. PLoS ONE 8, e76657-e76657 https://doi.org/10.1371/journal.pone.0076657
  60. Hoffstrom BG, Kaplan A, Letso R et al (2012) Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteins. Nat Chem Biol 6, 900-906
  61. Forrester MT, Benhar M and Stamler JS (2006) Nitrosative stress in the ER: a new role for S-nitrosylation in neurodegenerative diseases. ACS Chem Biol 1, 355-358 https://doi.org/10.1021/cb600244c
  62. Andreu CI, Woehlbier U, Torres M et al (2012) Protein disulfide isomerases in neurodegeneration: from disease mechanisms to biomedical applications. FEBS Lett 586, 2826-2834 https://doi.org/10.1016/j.febslet.2012.07.023
  63. Shin BK, Wang H, Yim AM et al (2003) Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. J Biol Chem 278, 7607-7616 https://doi.org/10.1074/jbc.M210455200
  64. Rho JH, Roehrl MH and Wang JY (2009) Glycoproteomic analysis of human lung adenocarcinomas using glycoarrays and tandem mass spectrometry: differential expression and glycosylation patterns of vimentin and fetuin A isoforms. Protein J 28, 148-160 https://doi.org/10.1007/s10930-009-9177-0
  65. Zhang D, Tai LK, Wong LL, Chiu LL, Sethi SK and Koay ES (2005) Proteomic study reveals that proteins involved in metabolic and detoxification pathways are highly expressed in HER-2/neu-positive breast cancer. Mol Cell Proteomics 4, 1686-1696 https://doi.org/10.1074/mcp.M400221-MCP200
  66. Zong J, Guo C, Liu S et al (2012) Proteomic research progress in lymphatic metastases of cancers. Clin Transl Oncol 14, 21-30 https://doi.org/10.1007/s12094-012-0757-7
  67. Ramos FS, Serino LT, Carvalho CM et al (2015) PDIA3 and PDIA6 gene expression as an aggressiveness marker in primary ductal breast cancer. Genet Mol Res 14, 6960-6967 https://doi.org/10.4238/2015.June.26.4
  68. Xu X, Wei X, Ling Q et al (2011) Identification of two portal vein tumor thrombosis associated proteins in hepatocellular carcinoma: protein disulfide-isomerase A6 and apolipoprotein A-I. J Gastroenterol Hepatol 26, 1787-1794 https://doi.org/10.1111/j.1440-1746.2011.06796.x
  69. Uyy E, Suica VI, Boteanu RM et al (2016) Endoplasmic Reticulum Chaperones Are Potential Active Factors in Thyroid Tumorigenesis. J Proteome Res 15, 3377-3387 https://doi.org/10.1021/acs.jproteome.6b00567
  70. Tufo G, Jones AW, Wang Z et al (2014) The protein disulfide isomerases PDIA4 and PDIA6 mediate resistance to cisplatin-induced cell death in lung adenocarcinoma. Cell Death Differ 21, 685-695 https://doi.org/10.1038/cdd.2013.193
  71. Yu SJ, Won JK, Ryu HS et al (2014) A novel prognostic factor for hepatocellular carcinoma: protein disulfide isomerase. Korean J Intern Med 29, 580-587 https://doi.org/10.3904/kjim.2014.29.5.580
  72. Bartkowiak K, Effenberger KE, Harder S et al (2010) Discovery of a novel unfolded protein response phenotype of cancer stem/progenitor cells from the bone marrow of breast cancer patients. J Proteome Res 9, 3158-3168 https://doi.org/10.1021/pr100039d
  73. Higa A, Taouji S, Lhomond S et al (2016) Endoplasmic reticulum stress-activated transcription factor ATF6 requires the disulfide isomerase PDIA5 to modulate chemoresistance. Mol Cell Biol 34, 1839-1849
  74. Lovat PE, Corazzari M, Armstrong JL et al (2008) Increasing melanoma cell death using inhibitors of protein disulfide isomerases to abrogate survival responses to endoplasmic reticulum stress. Cancer Res 68, 5363-5369 https://doi.org/10.1158/0008-5472.CAN-08-0035
  75. Na KS, Park BC, Jang M et al (2007) Protein disulfide isomerase is cleaved by caspase-3 and -7 during apoptosis. Mol Cells 24, 261-267
  76. Xu S, Butkevich AN, Yamada R et al (2012) Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment. Proc Natl Acad Sci U S A 109, 16348-16353 https://doi.org/10.1073/pnas.1205226109
  77. Meng X, Leyva ML, Jenny M et al (2009) A rutheniumcontaining organometallic compound reduces tumor growth through induction of the endoplasmic reticulum stress gene CHOP. Cancer Res 69, 5458-5466 https://doi.org/10.1158/0008-5472.CAN-08-4408
  78. Zhang J, Yi M, Zha L et al (2016) Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells: Implications for Apoptosis. PLoS One 11, e0147218 https://doi.org/10.1371/journal.pone.0147218
  79. Willems SH, Tape CJ, Stanley PL et al (2010) Thiol isomerases negatively regulate the cellular shedding activity of ADAM17. Biochem J 428, 439-450 https://doi.org/10.1042/BJ20100179
  80. Benham AM (2012) The protein disulfide isomerase family: key players in health and disease. Antioxid Redox Signal 16, 781-789 https://doi.org/10.1089/ars.2011.4439
  81. Camargo LDL, Babelova A, Mieth A et al (2013) Endo-PDI is required for $TNF{\alpha}$-induced angiogenesis. Free Radic Biol Med 65, 1398-1407 https://doi.org/10.1016/j.freeradbiomed.2013.09.028
  82. Zhang D and Richardson DR (2011) Endoplasmic reticulum protein 29 (ERp29): An emerging role in cancer. Int J Biochem Cell Biol 43, 33-36 https://doi.org/10.1016/j.biocel.2010.09.019
  83. Zhang D and Putti TC (2010) Over-expression of ERp29 attenuates doxorubicin-induced cell apoptosis through up-regulation of Hsp27 in breast cancer cells. Exp Cell Res 316, 3522-3531 https://doi.org/10.1016/j.yexcr.2010.08.014
  84. Obacz J, Takacova M, Brychtova V et al (2015) The role of AGR2 and AGR3 in cancer: similar but not identical. Eur J Cell Biol 94, 139-147 https://doi.org/10.1016/j.ejcb.2015.01.002
  85. Brychtova V, Vojtesek B and Hrstka R (2011) Anterior gradient 2: a novel player in tumor cell biology. Cancer Lett 304, 1-7 https://doi.org/10.1016/j.canlet.2010.12.023
  86. Higa A, Mulot A, Delom F et al (2011) Role of prooncogenic protein disulfide isomerase (PDI) family member anterior gradient 2 (AGR2) in the control of endoplasmic reticulum homeostasis. J Biol Chem 286, 44855-44868 https://doi.org/10.1074/jbc.M111.275529
  87. Ryu J, Park SG, Lee PY et al (2013) Dimerization of pro-oncogenic protein Anterior Gradient 2 is required for the interaction with BiP/GRP78. Biochem Biophys Res Commun 430, 610-615 https://doi.org/10.1016/j.bbrc.2012.11.105
  88. Dong A, Wodziak D and Lowe AW (2015) Epidermal growth factor receptor (EGFR) signaling requires a specific endoplasmic reticulum thioredoxin for the post- translational control of receptor presentation to the cell surface. J Biol Chem 290, 8016-8027 https://doi.org/10.1074/jbc.M114.623207
  89. Chevet E, Fessart D, Delom F et al (2013) Emerging roles for the pro-oncogenic anterior gradient-2 in cancer development. Oncogene 32, 2499-2509 https://doi.org/10.1038/onc.2012.346
  90. Fessart D, Domblides C and Avril T (2016) Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties. eLife 30, 5

Cited by

  1. Greetings from the endoplasmic reticulum (ER): escaping ER thiol isomerases regulate thrombosis vol.16, pp.2, 2018, https://doi.org/10.1111/jth.13916
  2. The role of protein disulphide isomerase AGR2 in the tumour niche pp.02484900, 2018, https://doi.org/10.1111/boc.201800024
  3. and experimental methods vol.8, pp.33, 2018, https://doi.org/10.1039/C8RA02683A