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Endoplasmic reticulum stress and apoptosis


Cell death is an essential event in normal life and development, as well as in the pathophysiological processes that lead to disease. It has become clear that each of the main cellular organelles can participate in cell death signalling pathways, and recent advances have highlighted the importance of the endoplasmic reticulum (ER) in cell death processes. In cells, the ER functions as the organelle where proteins mature, and as such, is very responsive to extracellular-intracellular changes of environment. This short overview focuses on the known pathways of programmed cell death triggering from or involving the ER.



activating transcription factor 6


B-cell receptorassociated protein 31


luminal binding protein


CCAAT/enhancerbinding proteins


eukaryotic translation initiation factor


ER overloaded response


endoplasmic reticulum

GADD 153:

growth arrest and DNA damage


general control of amino acid biosynthesis kinase


glucose-regulated protein family


glycogen synthetase kinase-3β


hemin-regulated inhibitor of protein synthesis


inositol 1,4,5-trisphosphate


inositolrequiring gene-1


interferon regulatory factor 1


mouse embryonic fibroblasts


nuclear factor-κB


protein disulphide isomerase


PKR-like ER kinase




activated protein kinase

PS1, 2:



sterol-regulatory element-binding proteins

SRP 72:

72 kDa component of SRP (signal recognition particle)


unfolded protein response


X-Box protein-1


  1. 1.

    Kaufman, R.J. Stress signalling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev. 13 (1999) 1211–1233.

    PubMed  CAS  Google Scholar 

  2. 2.

    Pahl, H.L. Signal transduction from the endoplasmic reticulum to the cell nucleus. Physiol. Rev. 79 (1999) 683–701.

    PubMed  CAS  Google Scholar 

  3. 3.

    Ma, Y. and Hendershot, L.M. The role of the unfolded protein response in tumour development: friend or foe? Nat. Rev. Cancer 4 (2004) 966–977.

    PubMed  CAS  Article  Google Scholar 

  4. 4.

    Lemasters, J.J. Dying a thousand deaths: redundant pathways from different organelles to apoptosis and necrosis. Gastroenterology 129 (2005) 351–360.

    PubMed  Article  Google Scholar 

  5. 5.

    Breckenridge, D.G., Germain, M., Mathai, J.P., Nguyen, M. and Shore, G.C. Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 22 (2003) 8608–8618.

    PubMed  CAS  Article  Google Scholar 

  6. 6.

    Scheuner, D., Song, B., McEwen, E., Liu, C., Laybutt, R., Gillespie, P., Saunders, T., Bonner-Weir, S. and Kaufman, R.J. Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol. Cell. 7 (2001) 1165–1176.

    PubMed  CAS  Article  Google Scholar 

  7. 7.

    Iwakoshi, N.N., Lee, A.H., Vallabhajosyula, P., Otipoby, K.L., Rajewsky, K. and Glimcher, L.H. Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat. Immunol. 4 (2003) 321–329.

    PubMed  CAS  Article  Google Scholar 

  8. 8.

    Gass, J.N., Gifford, N.M. and Brewer, J.W. Activation of an unfolded protein response during differentiation of antibody-secreting B cells. J. Biol. Chem. 277 (2002) 49047–49054.

    PubMed  CAS  Article  Google Scholar 

  9. 9.

    Reimold, A.M., Etkin, A., Clauss, I., Perkins, A., Friend, D.S., Zhang, J., Horton, H.F., Scott, A., Orkin, S.H., Byrne, M.C., Grusby, M.J. and Glimcher, L.H. An essential role in liver development for transcription factor XBP-1. Genes Dev. 14 (2000) 152–157.

    PubMed  CAS  Google Scholar 

  10. 10.

    Freiden, P.J., Gaut, J.R. and Hendershot, L.M. Interconversion of three differentially modified and assembled forms of BiP. EMBO J. 11 (1992) 63–70.

    PubMed  CAS  Google Scholar 

  11. 11.

    Blond-Elguindi, S., Fourie, A.M., Sambrook, J.F. and Gething, M.J. Peptide-dependent stimulation of the ATPase activity of the molecular chaperone BiP is the result of conversion of oligomers to active monomers. J. Biol. Chem. 268 (1993) 12730–12735.

    PubMed  CAS  Google Scholar 

  12. 12.

    Tirasophon, W., Welihinda, A.A. and Kaufman, R.J. A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev. 12 (1998) 1812–1824.

    PubMed  CAS  Google Scholar 

  13. 13.

    Wang, X.Z., Harding, H.P., Zhang, Y., Jolicoeur, E.M., Kuroda, M. and Ron, D. Cloning of mammalian Ire1 reveals diversity in the ER stress responses. EMBO J. 17 (1998a) 5708–5717.

    PubMed  CAS  Article  Google Scholar 

  14. 14.

    Ma, Y. and Hendershot, L.M. The unfolding tale of the unfolded protein response. Cell 107 (2001) 827–830

  15. 15.

    Shen, X., Ellis, R.E., Lee, K., Liu, C.Y., Yang, K., Solomon, A., Yoshida, H., Morimoto, R., Kurnit, D.M., Mori, K. and Kaufman, R.J. Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development. Cell 107 (2001) 893–903.

    PubMed  CAS  Article  Google Scholar 

  16. 16.

    Lee, K., Tirasophon, W., Shen, X., Michalak, M., Prywes, R., Okada, T., Yoshida, H., Mori, K. and Kaufman, R.J. IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev. 16 (2002) 452–466.

    PubMed  CAS  Article  Google Scholar 

  17. 17.

    Harding, H.P., Zhang, Y. and Ron, D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397 (1999) 271–274.

    PubMed  CAS  Article  Google Scholar 

  18. 18.

    Shi, Y., Vattem, K.M., Sood, R., An, J., Liang, J., Stramm, L. and Wek, R.C. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Mol. Cell. Biol. 18 (1998) 7499–74509.

    PubMed  CAS  Google Scholar 

  19. 19.

    Jiang, H.Y. and Wek, R.C. Phosphorylation of the alpha-subunit of the eukaryotic initiation factor-2 (eIF2alpha) reduces protein synthesis and enhances apoptosis in response to proteasome inhibition. J. Biol. Chem. 280 (2005) 14189–14202.

    PubMed  CAS  Article  Google Scholar 

  20. 20.

    Ye, J., Rawson, R.B., Komuro, R., Chen, X., Dave, U.P., Prywes, R., Brown, M.S. and Goldstein, J.L. ER stress induces cleavage of membranebound ATF6 by the same proteases that process SREBPs. Mol. Cell. 6 (2000) 1355–1364.

    PubMed  CAS  Article  Google Scholar 

  21. 21.

    Yoshida, H., Matsui, T., Yamamoto, A., Okada, T. and Mori, K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107 (2001) 881–891.

    PubMed  CAS  Article  Google Scholar 

  22. 22.

    Calfon, M., Zeng, H., Urano, F., Till, J.H., Hubbard, S.R., Harding, H.P., Clark, S.G. and Ron, D. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415 (2002) 92–96.

    PubMed  CAS  Article  Google Scholar 

  23. 23.

    Fornace, A.J. Jr., Alamo, I. Jr. and Hollander, M.C. DNA damage-inducible transcripts in mammalian cells. Proc. Natl. Acad. Sci. USA 85 (1988) 8800–8804.

    PubMed  CAS  Article  Google Scholar 

  24. 24.

    Ron, D. and Habener, J.F. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev. 6 (1992) 439–453.

    PubMed  CAS  Google Scholar 

  25. 25.

    Barone, M.V., Crozat, A., Tabaee, A., Philipson, L. and Ron, D. CHOP (GADD153) and its oncogenic variant, TLS-CHOP, have opposing effects on the induction of G1/S arrest. Genes Dev. 8 (1994) 453–464.

    PubMed  CAS  Google Scholar 

  26. 26.

    Zhan, Q., Lord, K.A., Alamo, I. Jr., Hollander, M.C., Carrier, F., Ron, D., Kohn, K.W., Hoffman, B., Liebermann, D.A. and Fornace, A.J. Jr. The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth. Mol. Cell. Biol. 14 (1994) 2361–2371.

    PubMed  CAS  Google Scholar 

  27. 27.

    Harding, H.P., Novoa, I., Zhang, Y., Zeng, H., Wek, R., Schapira, M. and Ron, D. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol. Cell. 6 (2000) 1099–108.

    PubMed  CAS  Article  Google Scholar 

  28. 28.

    Okada, T., Yoshida, H., Akazawa, R., Negishi, M. and Mori, K. Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response. Biochem. J. 366 (2002) 585–594.

    PubMed  CAS  Article  Google Scholar 

  29. 29.

    Wang, X.Z. and Ron, D. Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP Kinase. Science 272 (1996) 1347–1349.

    PubMed  CAS  Article  Google Scholar 

  30. 30.

    Oyadomari, S. and Mori, M. Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 11 (2004) 381–389.

    PubMed  CAS  Article  Google Scholar 

  31. 31.

    Wang, X.Z., Lawson, B., Brewer, J.W., Zinszner, H., Sanjay, A., Mi, L.J., Boorstein, R., Kreibich, G., Hendershot, L.M. and Ron, D. Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Mol. Cell. Biol. 16 (1996) 4273–4280.

    PubMed  CAS  Google Scholar 

  32. 32.

    Prostko, C.R., Brostrom, M.A., Malara, E.M. and Brostrom, C.O. Phosphorylation of eukaryotic initiation factor (eIF) 2 alpha and inhibition of eIF-2B in GH3 pituitary cells by perturbants of early protein processing that induce GRP78. J. Biol. Chem. 267 (1992) 16751–16754.

    PubMed  CAS  Google Scholar 

  33. 33.

    Samuel, C.E., Kuhen, K.L., George, C.X., Ortega, L.G., Rende-Fournier, R. and Tanaka, H. The PKR protein kinase—an interferon-inducible regulator of cell growth and differentiation. Int. J. Hematol. 65 (1997) 227–237.

    PubMed  CAS  Article  Google Scholar 

  34. 34.

    St Johnston, D., Brown, N.H., Gall, J.G. and Jantsch, M. A conserved double-stranded RNA-binding domain. Proc. Natl. Acad. Sci. USA 89 (1992) 10979–10983.

    PubMed  CAS  Article  Google Scholar 

  35. 35.

    Zinn, K., Keller, A., Whittemore, L.A. and Maniatis, T. 2-Aminopurine selectively inhibits the induction of beta-interferon, c-fos, and c-myc gene expression. Science 240 (1988) 210–213.

    PubMed  CAS  Article  Google Scholar 

  36. 36.

    Kumar, A., Haque, J., Lacoste, J., Hiscott, J. and Williams, B.R. Doublestranded RNA-dependent protein kinase activates transcription factor NFkappa B by phosphorylating I kappa B. Proc. Natl. Acad. Sci. USA 91 (1994) 6288–6292.

    PubMed  CAS  Article  Google Scholar 

  37. 37.

    Jimenez-Garcia, L.F., Green, S.R., Mathews, M.B. and Spector, D.L. Organization of the double-stranded RNA-activated protein kinase DAI and virus-associated VA RNAI in adenovirus-2-infected HeLa cells. J. Cell Sci. 106 (1993) 11–22.

    PubMed  CAS  Google Scholar 

  38. 38.

    Jeffrey, I.W., Kadereit, S., Meurs, E.F., Metzger, T., Bachmann, M., Schwemmle, M., Hovanessian, A.G. and Clemens, M.J. Nuclear localization of the interferon-inducible protein kinase PKR in human cells and transfected mouse cells. Exp. Cell Res. 218 (1995) 17–27.

    PubMed  CAS  Article  Google Scholar 

  39. 39.

    Wu, S., Kumar, K.U. and Kaufman, R.J. Identification and requirement of three ribosome binding domains in dsRNA-dependent protein kinase (PKR). Biochemistry 37 (1998) 13816–13826.

    PubMed  CAS  Article  Google Scholar 

  40. 40.

    Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B.A. and Yuan, J. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403 (2000) 98–103.

    PubMed  CAS  Article  Google Scholar 

  41. 41.

    Fischer, H., Koenig, U., Eckhart, L. and Tschachler, E. Human caspase 12 has acquired deleterious mutations. Biochem. Biophys. Res. Commun. 293 (2002) 722–726.

    PubMed  CAS  Article  Google Scholar 

  42. 42.

    Hitomi, J., Katayama, T., Eguchi, Y., Kudo, T., Taniguchi, M., Koyama, Y., Manabe, T., Yamagishi, S., Bando, Y., Imaizumi, K., Tsujimoto, Y. and Tohyama, M. Involvement of caspase-4 in endoplasmic reticulum stressinduced apoptosis and Abeta-induced cell death. J. Cell Biol. 165 (2004) 347–356.

    PubMed  CAS  Article  Google Scholar 

  43. 43.

    Urano, F., Wang, X., Bertolotti, A., Zhang, Y., Chung, P., Harding, H.P. and Ron, D. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287 (2000) 664–666.

    PubMed  CAS  Article  Google Scholar 

  44. 44.

    Yoneda, T., Imaizumi, K., Oono, K., Yui, D., Gomi, F., Katayama, T. and Tohyama, M. Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J. Biol. Chem. 276 (2001) 3935–3940.

    Google Scholar 

  45. 45.

    Rao, R.V., Castro-Obregon, S., Frankowski, H., Schuler, M., Stoka, V., del Rio, G., Bredesen, D.E. and Ellerby, H.M. Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway. J. Biol. Chem. 277 (2002) 21836–21842.

    PubMed  CAS  Article  Google Scholar 

  46. 46.

    Morishima, N., Nakanishi, K., Takenouchi, H., Shibata, T. and Yasuhiko, Y. An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. J. Biol. Chem. 277 (2002) 34287–34294.

    PubMed  CAS  Article  Google Scholar 

  47. 47.

    Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B.A. and Yuan J. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403 (2000) 98–103.

    PubMed  CAS  Article  Google Scholar 

  48. 48.

    Di Sano, F., Ferraro, E., Tufi, R., Achsel, T., Piacentini, M. and Cecconi, F. Endoplasmic reticulum stress induces apoptosis by an apoptosomedependent but caspase 12-independent mechanism. J. Biol. Chem. 281 (2006) 2693–2700.

    PubMed  Article  Google Scholar 

  49. 49.

    Saleh, M., Mathison, J.C., Wolinski, M.K., Bensinger, S.J., Fitzgerald, P., Droin, N., Ulevitch, R.J., Green, D.R. and Nicholson, D.W. Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. Nature 440 (2006) 1064–1068.

    PubMed  CAS  Article  Google Scholar 

  50. 50.

    Saleh, M., Vaillancourt, J.P., Graham, R.K., Huyck, M., Srinivasula, S.M., Alnemri, E.S., Steinberg, M.H., Nolan, V., Baldwin, C.T., Hotchkiss, R.S., Buchman, T.G., Zehnbauer, B.A., Hayden, M.R., Farrer, L.A., Roy, S. and Nicholson, D.W. Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms. Nature 6 (2004) 75–79.

    Article  Google Scholar 

  51. 51.

    Pahl, H.L. and Baeuerle, P.A. A novel signal transduction pathway from the endoplasmic reticulum to the nucleus is mediated by transcription factor NFkappa B. EMBO J. 14 (1995) 2580–2588.

    PubMed  CAS  Google Scholar 

  52. 52.

    Pahl, H.L., Sester, M., Burgert, H.G. and Baeuerle, P.A. Activation of transcription factor NF-kappaB by the adenovirus E3/19K protein requires its ER retention. J. Cell Biol. 132 (1996) 511–522.

    PubMed  CAS  Article  Google Scholar 

  53. 53.

    Hacki, J., Egger, L., Monney, L., Conus, S., Rosse, T., Fellay, I. and Borner, C. Apoptotic crosstalk between the endoplasmic reticulum and mitochondria controlled by Bcl-2. Oncogene 19 (2000) 2286–2295.

    PubMed  CAS  Article  Google Scholar 

  54. 54.

    Boya, P., Cohen, I., Zamzami, N., Vieira, H.L. and Kroemer, G. Endoplasmic reticulum stress-induced cell death requires mitochondrial membrane permeabilization. Cell Death Differ. 9 (2002) 465–467.

    PubMed  CAS  Article  Google Scholar 

  55. 55.

    McCormick, T.S., McColl, K.S. and Distelhorst, C.W. Mouse lymphoma cells destined to undergo apoptosis in response to thapsigargin treatment fail to generate a calcium-mediated grp78/grp94 stress response. J. Biol. Chem. 272 (1997) 6087–6092.

    PubMed  CAS  Article  Google Scholar 

  56. 56.

    McCullough, K.D., Martindale, J.L., Klotz, L.O., Aw, T.Y. and Holbrook, N.J. Gadd153 sensitizes cells to endoplasmic reticulum stress by downregulating Bcl2 and perturbing the cellular redox state. Mol. Cell. Biol. 21 (2001) 1249–1259.

    PubMed  CAS  Article  Google Scholar 

  57. 57.

    Wei, M.C., Zong, W.X., Cheng, E.H., Lindsten, T., Panoutsakopoulou, V., Ross, A.J., Roth, K.A., MacGregor, G.R., Thompson, C.B. and Korsmeyer, S.J. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292 (2001) 727–730.

    PubMed  CAS  Article  Google Scholar 

  58. 58.

    Rizzuto, R., Pinton, P., Carrington, W., Fay, F.S., Fogarty, K.E., Lifshitz, L.M., Tuft, R.A. and Pozzan, T. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 280 (1998) 1763–1766.

    PubMed  CAS  Article  Google Scholar 

  59. 59.

    Hsu, Y.T., Wolter, K.G. and Youle, R.J. Cytosol-to-membrane redistribution of Bax and Bcl-X(L) during apoptosis. Proc. Natl. Acad. Sci. USA 94 (1997) 3668–3672.

    PubMed  CAS  Article  Google Scholar 

  60. 60.

    Lindsten, T., Ross A.J., King, A., Zong, W.X., Rathmell, J.C., Shiels, H.A., Ulrich, E., Waymire, K.G., Mahar, P., Frauwirth, K., Chen, Y., Wei, M., Eng, V.M., Adelman, D.M., Simon, M.C., Ma, A., Golden, J.A., Evan, G., Korsmeyer, S.J., MacGregor, G.R. and Thompson, C.B. The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol. Cell. 6 (2000) 1389–1399.

    PubMed  CAS  Article  Google Scholar 

  61. 61.

    Zong, W.X., Lindsten, T., Ross, A.J., MacGregor, G.R. and Thompson, C.B. BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev. 15 (2001) 1481–1486.

    PubMed  CAS  Article  Google Scholar 

  62. 62.

    Pinton, P., Ferrari, D., Magalhaes, P., Schulze-Osthoff, K., Di Virgilio, F., Pozzan, T. and Rizzuto, R. Reduced loading of intracellular Ca2+ stores and downregulation of capacitative Ca2+ influx in Bcl-2-overexpressing cells. J. Cell Biol. 148 (2000) 857–862.

    PubMed  CAS  Article  Google Scholar 

  63. 63.

    Foyouzi-Youssefi, R., Arnaudeau, S., Borner, C., Kelley, W.L., Tschopp, J., Lew, D.P., Demaurex, N. and Krause, K.H. Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA 97 (2000) 5723–5728.

    PubMed  CAS  Article  Google Scholar 

  64. 64.

    Chami, M., Prandini, A., Campanella, M., Pinton, P., Szabadkai, G., Reed, J.C. and Rizzuto, R. Bcl-2 and Bax exert opposing effects on Ca2+ signaling, which do not depend on their putative pore-forming region. J. Biol. Chem. 279 (2004) 54581–54589.

    PubMed  CAS  Article  Google Scholar 

  65. 65.

    Li, H., Zhu, H., Xu, C.J. and Yuan, J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94 (1998) 491–501.

    PubMed  CAS  Article  Google Scholar 

  66. 66.

    Luo, X., Budihardjo, I., Zou, H., Slaughter, C. and Wang, X. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94 (1998) 481–490.

    PubMed  CAS  Article  Google Scholar 

  67. 67.

    Puthalakath, H. and Strasser, A. Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins. Cell Death Differ. 9 (2002) 505–512.

    PubMed  CAS  Article  Google Scholar 

  68. 68.

    Letai, A., Bassik, M.C., Walensky, L.D., Sorcinelli, M.D., Weiler, S. and Korsmeyer, S.J. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell. 2 (2002) 183–192.

    PubMed  CAS  Article  Google Scholar 

  69. 69.

    Germain, M., Mathai, J.P. and Shore, G.C. BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria. J. Biol. Chem. 277 (2002) 18053–18060.

    PubMed  CAS  Article  Google Scholar 

  70. 70.

    Ito, Y., Pandey, P., Mishra, N., Kumar, S., Narula, N., Kharbanda, S., Saxena, S. and Kufe, D. Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic reticulum stress-induced apoptosis. Mol. Cell. Biol. 21 (2001) 6233–6242.

    PubMed  CAS  Article  Google Scholar 

  71. 71.

    Ng, F.W., Nguyen, M., Kwan, T., Branton, P.E., Nicholson, D.W., Cromlish, J.A. and Shore, G.C. p28 Bap31, a Bcl-2/Bcl-XL-and procaspase-8-associated protein in the endoplasmic reticulum. J. Cell. Biol. 139 (1997) 327–338.

    PubMed  CAS  Article  Google Scholar 

  72. 72.

    Breckenridge, D.G., Nguyen, M., Kuppig, S., Reth, M. and Shore, G.C. The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA 99 (2002) 4331–4336.

    PubMed  CAS  Article  Google Scholar 

  73. 73.

    Nguyen, M., Breckenridge, D.G., Ducret, A. and Shore, G.C. Caspaseresistant BAP31 inhibits fas-mediated apoptotic membrane fragmentation and release of cytochrome c from mitochondria. Mol. Cell. Biol. 20 (2000) 6731–6740.

    PubMed  CAS  Article  Google Scholar 

  74. 74.

    Wang, X., Zelenski, N.G., Yang, J., Sakai, J., Brown, M.S. and Goldstein J.L. Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis. EMBO J. 15 (1996) 1012–1020.

    PubMed  CAS  Google Scholar 

  75. 75.

    Keenan, R.J., Freymann, D.M., Stroud, R.M. and Walter, P. The signal recognition particle. Annu. Rev. Biochem. 70 (2001) 755–775.

    PubMed  CAS  Article  Google Scholar 

  76. 76.

    Utz, P.J., Hottelet, M., Le, T.M., Kim, S.J., Geiger, M.E., van Venrooij, W.J. and Anderson P. The 72-kDa component of signal recognition particle is cleaved during apoptosis. J. Biol. Chem. 273 (1998) 35362–35370.

    PubMed  CAS  Article  Google Scholar 

  77. 77.

    Hirota, J., Furuichi, T. and Mikoshiba, K. Inositol 1,4,5-trisphosphate receptor type 1 is a substrate for caspase-3 and is cleaved during apoptosis in a caspase-3-dependent manner. J. Biol. Chem. 274 (1999) 34433–34437.

    PubMed  CAS  Article  Google Scholar 

  78. 78.

    Reddy, R.K., Lu, J. and Lee, A.S. The endoplasmic reticulum chaperone glycoprotein GRP94 with Ca (2+)-binding and antiapoptotic properties is a novel proteolytic target of calpain during etoposide-induced apoptosis. J. Biol. Chem. 274 (1999) 28476–28483.

    PubMed  CAS  Article  Google Scholar 

  79. 79.

    Wellington, C.L. and Hayden, M.R. Caspases and neurodegeneration: on the cutting edge of new therapeutic approaches. Clin. Genet. 57 (2000) 1–10.

    PubMed  CAS  Article  Google Scholar 

  80. 80.

    Qu, L., Huang, S., Baltzis, D., Rivas-Estilla, A.M., Pluquet, O., Hatzoglou, M., Koumenis, C., Taya, Y., Yoshimura, A. and Koromilas, A.E. Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3 beta. Genes Dev. 18 (2004) 261–277.

    PubMed  CAS  Article  Google Scholar 

  81. 81.

    Waterman, M.J., Stavridi, E.S., Waterman, J.L. and Halazonetis, T.D. ATMdependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins. Nat Genet. 19 (1998) 175–178.

    PubMed  CAS  Article  Google Scholar 

  82. 82.

    Stavridi, E.S., Chehab, N.H., Malikzay, A. and Halazonetis, T.D. Substitutions that compromise the ionizing radiation-induced association of p53 with 14-3-3 proteins also compromise the ability of p53 to induce cell cycle arrest. Cancer Res. 61 (2001) 7030–7033.

    PubMed  CAS  Google Scholar 

  83. 83.

    Bourdon, J.C., Deguin-Chambon, V., Lelong, J.C., Dessen, P., May, P., Debuire, B. and May, E. Further characterisation of the p53 responsive element identification of new candidate genes for trans-activation by p53. Oncogene 14 (1997) 85–94.

    PubMed  CAS  Article  Google Scholar 

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Correspondence to Borivoj Vojtesek.

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Faitova, J., Krekac, D., Hrstka, R. et al. Endoplasmic reticulum stress and apoptosis. Cell Mol Biol Lett 11, 488–505 (2006).

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Key words

  • Endoplasmic reticulum
  • Apoptosis
  • p53
  • Scotin