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Alternative Functions of the BCL-2 Protein Family at the Endoplasmic Reticulum

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BCL-2 Protein Family

Part of the book series: Advances in Experimental Medicine and Biology ((volume 687))

Abstract

Apoptosis is essential for maintenance of tissue homeostasis and its deregulation results in a variety of disease conditions. The BCL-2 family of proteins is a group of evolutionarily conserved regulators of cell death that comprises both anti- and pro-apoptotic members, that operate at the mitochondrial membrane to control caspase activation. Different BCL-2-related proteins are also located in the endoplasmic reticulum (ER), where important roles in organelle physiology are proposed. Adaptation to ER stress is mediated by the activation of a complex signal transduction pathway known as the unfolded protein response (UPR). Recent reports indicate that the ER stress sensor IRE1a, signals through the formation of a protein complex platform at the ER membrane, here termed the “UPRosome”. Alternatively, BCL-2 family members are contained in other multiprotein complexes at the ER that are involved in the control of diverse cellular processes including calcium homeostasis, autophagy and ER morphogenesis. Here we describe the emerging concept that BCL-2 family members are important regulators of essential cellular processes beyond apoptosis.

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References

  1. Ferri KF, Kroemer G. Organelle-specific initiation of cell death pathways. Nat Cell Biol 2001; 3(11):E255–63.

    Article  CAS  PubMed  Google Scholar 

  2. Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell 2004; 116(2):205–19.

    Article  CAS  PubMed  Google Scholar 

  3. Strasser A. The role of BH3-only proteins in the immune system. Nat Rev Immunol 2005; 5(3):189–200.

    Article  CAS  PubMed  Google Scholar 

  4. Zhang HM, Cheung P, Yanagawa B et al. BNips: a group of pro-apoptotic proteins in the BCL-2 family. Apoptosis 2003, 8(3):229–236.

    Article  CAS  PubMed  Google Scholar 

  5. Labi V, Erlacher M, Kiessling S et al. BH3-only proteins in cell death initiation, malignant disease and anticancer therapy. Cell Death Differ 2006, 13(8):1325–1338.

    Article  CAS  PubMed  Google Scholar 

  6. Wei MC, Zong WX, Cheng EH et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 2001, 292(5517):727–730.

    Article  CAS  PubMed  Google Scholar 

  7. Reed JC. Proapoptotic multidomain BCL-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities. Cell Death Differ 2006, 13(8):1378–1386.

    Article  CAS  PubMed  Google Scholar 

  8. Oakes SA, Lin SS, Bassik MC. The control of endoplasmic reticulum-initiated apoptosis by the BCL-2 family of proteins. Curr Mol Med 2006, 6(1):99–109.

    Article  CAS  PubMed  Google Scholar 

  9. Schroder M, Kaufman RJ. The mammalian unfolded protein response. Annu Rev Biochem 2005, 74:739–789.

    Article  PubMed  CAS  Google Scholar 

  10. Federovitch CM, Ron D, Hampton RY. The dynamic ER: experimental approaches and current questions. Curr Opin Cell Biol 2005, 17(4):409–414.

    Article  CAS  PubMed  Google Scholar 

  11. Rao RV, Bredesen DE. Misfolded proteins, endoplasmic reticulum stress and neurodegeneration. Curr Opin Cell Biol 2004, 16(6):653–662.

    Article  CAS  PubMed  Google Scholar 

  12. Koumenis C. ER stress, hypoxia tolerance and tumor progression. Curr Mol Med 2006, 6(1):55–69.

    Article  CAS  PubMed  Google Scholar 

  13. Lipson KL, Fonseca SG, Urano F. Endoplasmic reticulum stress-induced apoptosis and auto-immunity in diabetes. Curr Mol Med 2006, 6(1):71–77.

    Article  CAS  PubMed  Google Scholar 

  14. Hetz C, Glimcher L. The daily job of night killers: alternative roles of the BCL-2 family in organelle physiology. Trends Cell Biol 2008, 18(1):38–44.

    Article  CAS  PubMed  Google Scholar 

  15. Cox JS, Walter P. A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell 1996, 87(3):391–404.

    Article  CAS  PubMed  Google Scholar 

  16. Sidrauski C, Walter P. The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response. Cell 1997, 90(6):1031–1039.

    Article  CAS  PubMed  Google Scholar 

  17. Shamu CE, Walter P. Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus. EMBO J 1996, 15(12):3028–3039.

    CAS  PubMed  Google Scholar 

  18. Gonzalez TN, Walter P. Ire1p: a kinase and site-specific endoribonuclease. Methods Mol Biol 2001, 160:25–36.

    CAS  PubMed  Google Scholar 

  19. Lee K, Tirasophon W, Shen X et al. IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev 2002, 16(4):452–466.

    Article  CAS  PubMed  Google Scholar 

  20. Calfon M, Zeng H, Urano F et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 2002, 415(6867):92–96.

    Article  CAS  PubMed  Google Scholar 

  21. Yoshida H, Matsui T, Yamamoto A et al. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 2001, 107(7):881–891.

    Article  CAS  PubMed  Google Scholar 

  22. Lee AH, Iwakoshi NN, Glimcher LH. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol 2003, 23(21):7448–7459.

    Article  CAS  PubMed  Google Scholar 

  23. Reimold AM, Etkin A, Clauss I et al. An essential role in liver development for transcription factor XBP-1. Genes Dev 2000, 14(2):152–157.

    CAS  PubMed  Google Scholar 

  24. Reimold AM, Iwakoshi NN, Manis J et al. Plasma cell differentiation requires the transcription factor XBP-1. Nature 2001, 412(6844):300–307.

    Article  CAS  PubMed  Google Scholar 

  25. Iwakoshi NN, Lee AH, Vallabhajosyula P et al. Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat Immunol 2003, 4(4):321–329.

    Article  CAS  PubMed  Google Scholar 

  26. Lee AH, Chu GC, Iwakoshi NN et al. XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands. EMBO J 2005, 24(24):4368–4380.

    Article  CAS  PubMed  Google Scholar 

  27. Urano F, Wang X, Bertolotti A, Zhang Y et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 2000, 287(5453):664–666.

    Article  CAS  PubMed  Google Scholar 

  28. Nishitoh H, Matsuzawa A, Tobiume K et al. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev 2002, 16(11):1345–1355.

    Article  CAS  PubMed  Google Scholar 

  29. Nguyen DT, Kebache S, Fazel A et al. Nck-dependent activation of extracellular signal-regulated kinase-1 and regulation of cell survival during endoplasmic reticulum stress. Mol Biol Cell 2004, 15(9):4248–4260.

    Article  CAS  PubMed  Google Scholar 

  30. Gu F, Nguyen DT, Stuible M et al. Protein-tyrosine phosphatase 1B potentiates IRE1 signaling during endoplasmic reticulum stress. J Biol Chem 2004, 279(48):49689–49693.

    Article  CAS  PubMed  Google Scholar 

  31. Hu P, Han Z, Couvillon AD et al. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression. Mol Cell Biol 2006, 26(8):3071–3084.

    Article  CAS  PubMed  Google Scholar 

  32. Hetz CA, Soto C. Emerging roles of the unfolded protein response signaling in physiology and disease. Curr Mol Med 2006, 6(1):1.

    Article  CAS  PubMed  Google Scholar 

  33. Luo D, He Y, Zhang H et al. AIP1 is critical in transducing IRE1-mediated endoplasmic reticulum stress response. J Biol Chem 2008, 283(18):11905–11912.

    Article  CAS  PubMed  Google Scholar 

  34. Lin JH, Li H, Yasumura D, Cohen HR et al. IRE1 signaling affects cell fate during the unfolded protein response. Science 2007, 318(5852):944–949.

    Article  CAS  PubMed  Google Scholar 

  35. Kuwana T, Bouchier-Hayes L, Chipuk JE et al. BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol Cell 2005, 17(4):525–535.

    Article  CAS  PubMed  Google Scholar 

  36. Szegezdi E, Duffy A, O’Mahoney ME et al. ER stress contributes to ischemia-induced cardiomyocyte apoptosis. Biochem Biophys Res Commun 2006, 349(4):1406–1411.

    Article  CAS  PubMed  Google Scholar 

  37. Hetz C, Bernasconi P, Fisher J et al. Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha. Science 2006, 312(5773):572–576.

    Article  CAS  PubMed  Google Scholar 

  38. Klee M, Pallauf K, Alcala S, Fleischer A et al. Mitochondrial apoptosis induced by BH3-only molecules in the exclusive presence of endoplasmic reticular Bak. EMBO J 2009.

    Google Scholar 

  39. Xu Q, Reed JC. Bax inhibitor-1, a mammalian apoptosis suppressor identified by functional screening in yeast. Mol Cell 1998, 1(3):337–346.

    Article  CAS  PubMed  Google Scholar 

  40. Chae HJ, Ke N, Kim HR, Chen S et al. Evolutionarily conserved cytoprotection provided by Bax Inhibitor-1 homologs from animals, plants, and yeast. Gene 2003, 323:101–113.

    Article  CAS  PubMed  Google Scholar 

  41. Huckelhoven R. BAX Inhibitor-1, an ancient cell death suppressor in animals and plants with prokaryotic relatives. Apoptosis 2004, 9(3):299–307.

    Article  CAS  PubMed  Google Scholar 

  42. Chae HJ, Kim HR, Xu C et al. BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress. Mol Cell 2004, 15(3):355–366.

    Article  CAS  PubMed  Google Scholar 

  43. Bailly-Maitre B, Fondevila C, Kaldas F et al. Cytoprotective gene bi-1 is required for intrinsic protection from endoplasmic reticulum stress and ischemia-reperfusion injury. Proc Natl Acad Sci U S A 2006, 103(8):2809–2814.

    Article  CAS  PubMed  Google Scholar 

  44. Lee GH, Kim HK, Chae SW et al. Bax inhibitor-1 regulates endoplasmic reticulum stress-associated reactive oxygen species and heme oxygenase-1 expression. J Biol Chem 2007, 282(30):21618–21628.

    Article  CAS  PubMed  Google Scholar 

  45. Lisbona F, Rojas-Rivera D, Thielen P et al. BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha. Mol Cell 2009, 33(6):679–691.

    Article  CAS  PubMed  Google Scholar 

  46. Kawai-Yamada M, Ohori Y, Uchimiya H. Dissection of Arabidopsis Bax inhibitor-1 suppressing Bax-, hydrogen peroxide-, and salicylic acid-induced cell death. Plant Cell 2004, 16(1):21–32.

    Article  CAS  PubMed  Google Scholar 

  47. Hetz C, Bono MR, Barros LF, Lagos R. Microcin E492, a channel-forming bacteriocin from Klebsiella pneumoniae, induces apoptosis in some human cell lines. Proc Natl Acad Sci U S A 2002, 99(5):2696–2701.

    Article  CAS  PubMed  Google Scholar 

  48. Kim H, Rafiuddin-Shah M, Tu HC et al. Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies. Nat Cell Biol 2006, 8(12):1348–1358.

    Article  CAS  PubMed  Google Scholar 

  49. Willis SN, Fletcher JI, Kaufmann T et al. Apoptosis initiated when BH3 ligands engage multiple BCL-2 homologs, not Bax or Bak. Science 2007, 315(5813):856–859.

    Article  CAS  PubMed  Google Scholar 

  50. Letai A, Bassik MC, Walensky LD et al. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2002, 2(3):183–192.

    Article  CAS  PubMed  Google Scholar 

  51. Li J, Lee B, Lee AS. Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53. J Biol Chem 2006, 281(11):7260–7270.

    Article  CAS  PubMed  Google Scholar 

  52. Reimertz C, Kogel D, Rami A et al. Gene expression during ER stress-induced apoptosis in neurons: induction of the BH3-only protein Bbc3/PUMA and activation of the mitochondrial apoptosis pathway. J Cell Biol 2003, 162(4):587–597.

    Article  CAS  PubMed  Google Scholar 

  53. Futami T, Miyagishi M, Taira K. Identification of a network involved in thapsigargin-induced apoptosis using a library of small interfering RNA expression vectors. J Biol Chem 2005, 280(1):826–831.

    CAS  PubMed  Google Scholar 

  54. Jiang CC, Lucas K, Avery-Kiejda KA et al. Up-regulation of Mcl-1 is critical for survival of human melanoma cells upon endoplasmic reticulum stress. Cancer Res 2008, 68(16):6708–6717.

    Article  CAS  PubMed  Google Scholar 

  55. Wang Q, Mora-Jensen H, Weniger MA et al. ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells. Proc Natl Acad Sci U S A 2009, 106(7):2200–2205.

    Article  CAS  PubMed  Google Scholar 

  56. Germain M, Mathai JP, Shore GC. BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria. J Biol Chem 2002, 277(20):18053–18060.

    Article  CAS  PubMed  Google Scholar 

  57. Mathai JP, Germain M, Shore GC. BH3-only BIK regulates BAX,BAK-dependent release of Ca2+ from endoplasmic reticulum stores and mitochondrial apoptosis during stress-induced cell death. J Biol Chem 2005, 280(25):23829–23836.

    Article  CAS  PubMed  Google Scholar 

  58. Puthalakath H, O’Reilly LA, Gunn P et al. ER stress triggers apoptosis by activating BH3-only protein Bim. Cell 2007, 129(7):1337–1349.

    Article  CAS  PubMed  Google Scholar 

  59. Morishima N, Nakanishi K, Tsuchiya K et al. Translocation of Bim to the endoplasmic reticulum (ER) mediates ER stress signaling for activation of caspase-12 during ER stress-induced apoptosis. J Biol Chem 2004, 279(48):50375–50381.

    Article  CAS  PubMed  Google Scholar 

  60. Elyaman W, Terro F, Suen KC et al. BAD and BCL-2 regulation are early events linking neuronal endoplasmic reticulum stress to mitochondria-mediated apoptosis. Brain Res Mol Brain Res 2002, 109(1–2):233–238.

    Article  CAS  PubMed  Google Scholar 

  61. Upton JP, Austgen K, Nishino M et al. Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress. Mol Cell Biol 2008, 28(12):3943–3951.

    Article  CAS  PubMed  Google Scholar 

  62. Scorrano L, Oakes SA, Opferman JT et al. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science 2003, 300(5616):135–139.

    Article  CAS  PubMed  Google Scholar 

  63. Zong WX, Li C, Hatzivassiliou G et al. Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J Cell Biol 2003, 162(1):59–69.

    Article  CAS  PubMed  Google Scholar 

  64. Bassik MC, Scorrano L, Oakes SA et al. Phosphorylation of BCL-2 regulates ER Ca2+ homeostasis and apoptosis. EMBO J 2004, 23(5):1207–1216.

    Article  CAS  PubMed  Google Scholar 

  65. Breckenridge DG, Germain M, Mathai JP et al. Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 2003, 22(53):8608–8618.

    Article  CAS  PubMed  Google Scholar 

  66. Pinton P, Rizzuto R. BCL-2 and Ca2+ homeostasis in the endoplasmic reticulum. Cell Death Differ 2006, 13(8):1409–1418.

    Article  CAS  PubMed  Google Scholar 

  67. Xu C, Xu W, Palmer AE, Reed JC. BI-1 regulates endoplasmic reticulum Ca2+ homeostasis downstream of BCL-2 family proteins. J Biol Chem 2008, 283(17):11477–11484.

    Article  CAS  PubMed  Google Scholar 

  68. Westphalen BC, Wessig J, Leypoldt F et al. BI-1 protects cells from oxygen glucose deprivation by reducing the calcium content of the endoplasmic reticulum. Cell Death Differ 2005, 12(3):304–306.

    Article  CAS  PubMed  Google Scholar 

  69. Oakes SA, Scorrano L, Opferman JT et al. Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc Natl Acad Sci U S A 2005, 102(1):105–110.

    Article  CAS  PubMed  Google Scholar 

  70. Chen R, Valencia I, Zhong F, McColl KS et al. BCL-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate. J Cell Biol 2004, 166(2):193–203.

    Article  CAS  PubMed  Google Scholar 

  71. White C, Li C, Yang J, Petrenko NB et al. The endoplasmic reticulum gateway to apoptosis by Bcl-X(L) modulation of the InsP3R. Nat Cell Biol 2005, 7(10):1021–1028.

    Article  CAS  PubMed  Google Scholar 

  72. Lin SS, Bassik MC, Suh H et al. PP2A regulates BCL-2 phosphorylation and proteasome-mediated degradation at the endoplasmic reticulum. J Biol Chem 2006, 281(32):23003–23012.

    Article  CAS  PubMed  Google Scholar 

  73. Dremina ES, Sharov VS, Kumar K et al. Anti-apoptotic protein BCL-2 interacts with and destabilizes the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA). Biochem J 2004, 383(Pt 2):361–370.

    CAS  PubMed  Google Scholar 

  74. Dremina ES, Sharov VS, Schoneich C. Displacement of SERCA from SR lipid caveolae-related domains by BCL-2: a possible mechanism for SERCA inactivation. Biochemistry 2006, 45(1):175–184.

    Article  CAS  PubMed  Google Scholar 

  75. Levine B. Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell 2005, 120(2):159–162.

    CAS  PubMed  Google Scholar 

  76. Cuervo AM. Autophagy: in sickness and in health. Trends Cell Biol 2004, 14(2):70–77.

    Article  PubMed  CAS  Google Scholar 

  77. Aita VM, Liang XH, Murty VV et al. Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics 1999, 59(1):59–65.

    Article  CAS  PubMed  Google Scholar 

  78. Liang XH, Jackson S, Seaman M et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999, 402(6762):672–676.

    Article  CAS  PubMed  Google Scholar 

  79. Qu X, Yu J, Bhagat G, Furuya N et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 2003, 112(12):1809–1820.

    CAS  PubMed  Google Scholar 

  80. Yue Z, Jin S, Yang C, Levine AJ et al. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci U S A 2003, 100(25):15077–15082.

    Article  CAS  PubMed  Google Scholar 

  81. Pattingre S, Tassa A, Qu X et al. BCL-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005, 122(6):927–939.

    Article  CAS  PubMed  Google Scholar 

  82. Ciechomska IA, Goemans GC, Skepper JN et al. BCL-2 complexed with Beclin-1 maintains full anti-apoptotic function. Oncogene 2009, 28(21):2128–2141.

    Article  CAS  PubMed  Google Scholar 

  83. Maiuri MC, Le Toumelin G, Criollo A et al. Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J 2007, 26(10):2527–2539.

    Article  CAS  PubMed  Google Scholar 

  84. Maiuri MC, Criollo A, Tasdemir E et al. BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and BCL-2/Bcl-X(L). Autophagy 2007, 3(4):374–376.

    CAS  PubMed  Google Scholar 

  85. Wei Y, Pattingre S, Sinha S et al. JNK1-mediated phosphorylation of BCL-2 regulates starvation-induced autophagy. Mol Cell 2008, 30(6):678–688.

    Article  CAS  PubMed  Google Scholar 

  86. Criollo A, Vicencio JM, Tasdemir E et al. The inositol trisphosphate receptor in the control of autophagy. Autophagy 2007, 3(4):350–353.

    CAS  PubMed  Google Scholar 

  87. Criollo A, Maiuri MC, Tasdemir E et al. Regulation of autophagy by the inositol trisphosphate receptor. Cell Death Differ 2007, 14(5):1029–1039.

    CAS  PubMed  Google Scholar 

  88. Hoyer-Hansen M, Bastholm L, Szyniarowski P et al. Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and BCL-2. Mol Cell 2007, 25(2):193–205.

    Article  PubMed  CAS  Google Scholar 

  89. Hoyer-Hansen M, Jaattela M. Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ 2007, 14(9):1576–1582.

    Article  CAS  PubMed  Google Scholar 

  90. Kouroku Y, Fujita E, Tanida I et al. ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ 2007, 14(2):230–239.

    Article  CAS  PubMed  Google Scholar 

  91. Ogata M, Hino S, Saito A et al. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 2006, 26(24):9220–9231.

    Article  CAS  PubMed  Google Scholar 

  92. Yorimitsu T, Nair U, Yang Z et al. Endoplasmic reticulum stress triggers autophagy. J Biol Chem 2006, 281(40):30299–30304.

    Article  CAS  PubMed  Google Scholar 

  93. Bernales S, McDonald KL, Walter P. Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLoS Biol 2006, 4(12):e423.

    Article  PubMed  CAS  Google Scholar 

  94. Ding WX, Ni HM, Gao W et al. Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival. J Biol Chem 2007, 282(7):4702–4710.

    Article  CAS  PubMed  Google Scholar 

  95. Ding WX, Ni HM, Gao W et al. Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am J Pathol 2007, 171(2):513–524.

    Article  CAS  PubMed  Google Scholar 

  96. Klee M, Pimentel-Muinos FX. Bcl-X(L) specifically activates Bak to induce swelling and restructuring of the endoplasmic reticulum. J Cell Biol 2005, 168(5):723–734.

    Article  CAS  PubMed  Google Scholar 

  97. Karbowski M, Norris KL, Cleland MM et al. Role of Bax and Bak in mitochondrial morphogenesis. Nature 2006, 443(7112):658–662.

    Article  CAS  PubMed  Google Scholar 

  98. Nakajima K, Hirose H, Taniguchi M et al. Involvement of BNIP1 in apoptosis and endoplasmic reticulum membrane fusion. EMBO J 2004, 23(16):3216–3226.

    Article  CAS  PubMed  Google Scholar 

  99. de Brito OM, Scorrano L. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 2008, 456(7222):605–610.

    Article  PubMed  CAS  Google Scholar 

  100. Schuler M, Green DR. Transcription, apoptosis and p53: catch-22. Trends Genet 2005, 21(3):182–187.

    Article  CAS  PubMed  Google Scholar 

  101. Zinkel S, Gross A, Yang E. BCL2 family in DNA damage and cell cycle control. Cell Death Differ 2006, 13(8):1351–1359.

    Article  CAS  PubMed  Google Scholar 

  102. Kamer I, Sarig R, Zaltsman Y et al. Proapoptotic BID is an ATM effector in the DNA-damage response. Cell 2005, 122(4):593–603.

    Article  CAS  PubMed  Google Scholar 

  103. Zinkel SS, Hurov KE, Ong C et al. A role for proapoptotic BID in the DNA-damage response. Cell 2005, 122(4):579–591.

    Article  CAS  PubMed  Google Scholar 

  104. Bruey JM, Bruey-Sedano N, Luciano F et al. BCL-2 and BCL-XL regulate proinflammatory caspase-1 activation by interaction with NALP1. Cell 2007, 129(1):45–56.

    Article  CAS  PubMed  Google Scholar 

  105. Danial NN, Gramm CF, Scorrano L et al. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 2003, 424(6951):952–956.

    Article  CAS  PubMed  Google Scholar 

  106. Danial NN, Walensky LD, Zhang CY et al. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat Med 2008, 14(2):144–153.

    Article  CAS  PubMed  Google Scholar 

  107. Holtz WA, O’Malley KL. Parkinsonian mimetics induce aspects of unfolded protein response in death of dopaminergic neurons. J Biol Chem 2003, 278(21):19367–19377.

    Article  CAS  PubMed  Google Scholar 

  108. Ryu EJ, Harding HP, Angelastro JM et al. Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson’s disease. J Neurosci 2002, 22(24):10690–10698.

    CAS  PubMed  Google Scholar 

  109. Ghribi O. The role of the endoplasmic reticulum in the accumulation of beta-amyloid peptide in Alzheimer’s disease. Curr Mol Med 2006, 6(1):119–133.

    Article  CAS  PubMed  Google Scholar 

  110. Hetz C, Russelakis-Carneiro M, Maundrell K et al. Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein. EMBO J 2003, 22(20):5435–5445.

    Article  CAS  PubMed  Google Scholar 

  111. Hetz C, Russelakis-Carneiro M, Walchli S et al. The disulfide isomerase Grp58 is a protective factor against prion neurotoxicity. J Neurosci 2005, 25(11):2793–2802.

    Article  CAS  PubMed  Google Scholar 

  112. Hetz CA, Soto C. Stressing out the ER: a role of the unfolded protein response in prion-related disorders. Curr Mol Med 2006, 6(1):37–43.

    Article  CAS  PubMed  Google Scholar 

  113. Turner BJ, Atkin JD. ER stress and UPR in familial amyotrophic lateral sclerosis. Curr Mol Med 2006, 6(1):79–86.

    Article  CAS  PubMed  Google Scholar 

  114. Momoi T. Conformational diseases and ER stress-mediated cell death: apoptotic cell death and autophagic cell death. Curr Mol Med 2006, 6(1):111–118.

    Article  CAS  PubMed  Google Scholar 

  115. Sekine Y, Takeda K, Ichijo H. The ASK1-MAP kinase signaling in ER stress and neurodegenerative diseases. Curr Mol Med 2006, 6(1):87–97.

    Article  CAS  PubMed  Google Scholar 

  116. Hetz C, Thielen P, Fisher J et al. The proapoptotic BCL-2 family member BIM mediates motoneuron loss in a model of amyotrophic lateral sclerosis. Cell Death Differ 2007, 14(7):1386–1389.

    Article  CAS  PubMed  Google Scholar 

  117. Oltersdorf T, Elmore SW, Shoemaker AR et al. An inhibitor of BCL-2 family proteins induces regression of solid tumours. Nature 2005, 435(7042):677–681.

    Article  CAS  PubMed  Google Scholar 

  118. Nguyen M, Marcellus RC, Roulston A et al. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc Natl Acad Sci U S A 2007, 104(49):19512–19517.

    Article  CAS  PubMed  Google Scholar 

  119. Hetz C, Vitte PA, Bombrun A, Rostovtseva TK et al. Bax channel inhibitors prevent mitochondrion-mediated apoptosis and protect neurons in a model of global brain ischemia. J Biol Chem 2005, 280(52):42960–42970.

    Article  CAS  PubMed  Google Scholar 

  120. Walensky LD, Kung AL, Escher I et al. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 2004, 305(5689):1466–1470.

    Article  CAS  PubMed  Google Scholar 

  121. Walensky LD, Pitter K, Morash J et al. A stapled BID BH3 helix directly binds and activates BAX. Mol Cell 2006, 24(2):199–210.

    Article  CAS  PubMed  Google Scholar 

  122. Letai A. Pharmacological manipulation of BCL-2 family members to control cell death. J Clin Invest 2005, 115(10):2648–2655.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Program of Cellular and Molecular Biology, The FONDAP Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile, P.O. BOX 70086

    Diego Rojas-Rivera, Benjamin Caballero, Sebastian Zamorano, Fernanda Lisbona & Claudio Hetz

  2. Millennium Nucleus for Neural Morphogenesis (NEMO), University of Chile, Santiago, Chile, P.O. BOX 70086

    Diego Rojas-Rivera, Benjamin Caballero, Sebastian Zamorano, Fernanda Lisbona & Claudio Hetz

Authors
  1. Diego Rojas-Rivera
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  2. Benjamin Caballero
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  3. Sebastian Zamorano
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  4. Fernanda Lisbona
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  5. Claudio Hetz
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Corresponding author

Correspondence to Claudio Hetz .

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Editors and Affiliations

  1. Institute of Biomedical Sciences, FONDAP Center for Molecular Studies of the Cell (CEMC) Millennium Nucleus for Neural Morphogenesis (NEMO), University of Chile, Santiago, Chile

    Claudio Hetz PhD

  2. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA

    Claudio Hetz PhD

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Rojas-Rivera, D., Caballero, B., Zamorano, S., Lisbona, F., Hetz, C. (2010). Alternative Functions of the BCL-2 Protein Family at the Endoplasmic Reticulum. In: Hetz, C. (eds) BCL-2 Protein Family. Advances in Experimental Medicine and Biology, vol 687. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6706-0_2

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