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Proapoptotic BAX and BAK Modulate the Unfolded Protein Response by a Direct Interaction with IRE1α

Science, 28 April 2006
Vol. 312, Issue 5773, p. 572-576
DOI: 10.1126/science.1123480

Proapoptotic BAX and BAK Modulate the Unfolded Protein Response by a Direct Interaction with IRE1α

  1. Claudio Hetz1,2,*,
  2. Paula Bernasconi1,
  3. Jill Fisher1,
  4. Ann-Hwee Lee2,
  5. Michael C. Bassik1,
  6. Bruno Antonsson4,
  7. Gabriel S. Brandt5,
  8. Neal N. Iwakoshi2,
  9. Anna Schinzel1,
  10. Laurie H. Glimcher2,3,*,
  11. Stanley J. Korsmeyer1,
  1. 1 Howard Hughes Medical Institute, Dana–Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA.
  2. 2 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
  3. 3 Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  4. 4 Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, 1228 Plan les Ouates, Switzerland.
  5. 5 Departments of Biochemistry and Chemistry, Rosenstiel Center, Brandeis University, Waltham, MA 02454, USA.
  1. * To whom correspondence should be addressed. E-mail: lglimche{at} (L.H.G.); chetz{at} (C.H.)
  • Deceased.


Accumulation of misfolded protein in the endoplasmic reticulum (ER) triggers an adaptive stress response—termed the unfolded protein response (UPR)—mediated by the ER transmembrane protein kinase and endoribonuclease inositol-requiring enzyme–1α (IRE1α). We investigated UPR signaling events in mice in the absence of the proapoptotic BCL-2 family members BAX and BAK [double knockout (DKO)]. DKO mice responded abnormally to tunicamycin-induced ER stress in the liver, with extensive tissue damage and decreased expression of the IRE1 substrate X-box–binding protein 1 and its target genes. ER-stressed DKO cells showed deficient IRE1α signaling. BAX and BAK formed a protein complex with the cytosolic domain of IRE1α that was essential for IRE1α activation. Thus, BAX and BAK function at the ER membrane to activate IRE1α signaling and to provide a physical link between members of the core apoptotic pathway and the UPR.

    • Received for publication 6 December 2005.
    • Accepted for publication 27 March 2006.


    C. Hetz, P. Bernasconi, J. Fisher, A.-H. Lee, M. C. Bassik, B. Antonsson, G. S. Brandt, N. N. Iwakoshi, A. Schinzel, L. H. Glimcher, and S. J. Korsmeyer, Proapoptotic BAX and BAK Modulate the Unfolded Protein Response by a Direct Interaction with IRE1α. Science 312, 572-576 (2006).

    The unfolded protein response is shaped by the NMD pathway
    R. Karam, C.-H. Lou, H. Kroeger, L. Huang, J. H. Lin, and M. F. Wilkinson
    EMBO Rep. 16, 599-609 (1 May 2015)

    Ask1 Gene Deletion Blocks Maternal Diabetes-Induced Endoplasmic Reticulum Stress in the Developing Embryo by Disrupting the Unfolded Protein Response Signalosome
    F. Wang, Y. Wu, H. Gu, E. A. Reece, S. Fang, R. Gabbay-Benziv, G. Aberdeen, and P. Yang
    Diabetes 64, 973-988 (1 March 2015)

    RNase L Interacts with Filamin A To Regulate Actin Dynamics and Barrier Function for Viral Entry
    K. Malathi, M. A. Siddiqui, S. Dayal, M. Naji, H. J. Ezelle, C. Zeng, A. Zhou, and B. A. Hassel
    mBio 5, e02012-14-e02012-14 (31 December 2014)

    Cellular Mechanisms of Endoplasmic Reticulum Stress Signaling in Health and Disease. 1. An overview
    E. Dufey, D. Sepulveda, D. Rojas-Rivera, and C. Hetz
    Am. J. Physiol. Cell Physiol. 307, C582-C594 (1 October 2014)

    Redox controls UPR to control redox
    D. Eletto, E. Chevet, Y. Argon, and C. Appenzeller-Herzog
    J. Cell Sci. 127, 3649-3658 (1 September 2014)

    Lipase Maturation Factor 1 (Lmf1) Is Induced by Endoplasmic Reticulum Stress Through Activating Transcription Factor 6{alpha} (Atf6{alpha}) Signaling
    H. Z. Mao, N. Ehrhardt, C. Bedoya, J. A. Gomez, D. DeZwaan-McCabe, I. N. Mungrue, R. J. Kaufman, D. T. Rutkowski, and M. Peterfy
    J Biol Chem 289, 24417-24427 (29 August 2014)

    Interplay Between the Oxidoreductase PDIA6 and microRNA-322 Controls the Response to Disrupted Endoplasmic Reticulum Calcium Homeostasis
    J. Groenendyk, Z. Peng, E. Dudek, X. Fan, M. J. Mizianty, E. Dufey, H. Urra, D. Sepulveda, D. Rojas-Rivera, Y. Lim et al.
    Sci Signal 7, ra54-ra54 (10 June 2014)

    Activated ERBB2/HER2 Licenses Sensitivity to Apoptosis upon Endoplasmic Reticulum Stress through a PERK-Dependent Pathway
    R. Martin-Perez, C. Palacios, R. Yerbes, A. Cano-Gonzalez, D. Iglesias-Serret, J. Gil, M. J. Reginato, and A. Lopez-Rivas
    Cancer Res. 74, 1766-1777 (15 March 2014)

    Inositol-requiring Enzyme 1 Inhibits Respiratory Syncytial Virus Replication
    I. Hassan, K. S. Gaines, W. J. Hottel, R. M. Wishy, S. E. Miller, L. S. Powers, D. T. Rutkowski, and M. M. Monick
    J Biol Chem 289, 7537-7546 (14 March 2014)

    Unfolded Protein Response Signaling and Metabolic Diseases
    J. Lee, and U. Ozcan
    J Biol Chem 289, 1203-1211 (17 January 2014)

    The Paradox of the Unfolded Protein Response in Cancer
    Anticancer Res 33, 4683-4694 (1 November 2013)

    Altered mitochondrial morphology and defective protein import reveal novel roles for Bax and/or Bak in skeletal muscle
    Y. Zhang, S. Iqbal, M. F. N. O'Leary, K. J. Menzies, A. Saleem, S. Ding, and D. A. Hood
    Am. J. Physiol. Cell Physiol. 305, C502-C511 (1 September 2013)

    Mfn2 modulates the UPR and mitochondrial function via repression of PERK
    J. P. Munoz, S. Ivanova, J. Sanchez-Wandelmer, P. Martinez-Cristobal, E. Noguera, A. Sancho, A. Diaz-Ramos, M. I. Hernandez-Alvarez, D. Sebastian, C. Mauvezin et al.
    EMBO J. 32, 2348-2361 (28 August 2013)

    Molecular mechanisms of neurodegeneration mediated by dysfunctional subcellular organelles in transmissible spongiform encephalopathies
    Z. Song, D. Zhao, and L. Yang
    Acta Biochim Biophys Sin 45, 452-464 (1 June 2013)

    Endoplasmic Reticulum Stress and the Unfolded Protein Response: Targeting the Achilles Heel of Multiple Myeloma
    L. Vincenz, R. Jager, M. O'Dwyer, and A. Samali
    Molecular Cancer Therapeutics 12, 831-843 (1 June 2013)

    Phenformin Activates the Unfolded Protein Response in an AMP-activated Protein Kinase (AMPK)-dependent Manner
    L. Yang, H. Sha, R. L. Davisson, and L. Qi
    J Biol Chem 288, 13631-13638 (10 May 2013)

    Xenobiotic Perturbation of ER Stress and the Unfolded Protein Response
    M. A. Lafleur, J. L. Stevens, and J. W. Lawrence
    Toxicol Pathol 41, 235-262 (1 February 2013)

    Impaired neurotransmission in ether lipid-deficient nerve terminals
    A. Brodde, A. Teigler, B. Brugger, W. D. Lehmann, F. Wieland, J. Berger, and W. W. Just
    Hum Mol Genet 21, 2713-2724 (15 June 2012)

    BH3-only proteins are part of a regulatory network that control the sustained signalling of the unfolded protein response sensor IRE1{alpha}
    D. A. Rodriguez, S. Zamorano, F. Lisbona, D. Rojas-Rivera, H. Urra, J. R. Cubillos-Ruiz, R. Armisen, D. R. Henriquez, E. H Cheng, M. Letek et al.
    EMBO J. 31, 2322-2335 (16 May 2012)

    Non-apoptotic functions of apoptosis-regulatory proteins
    L. Galluzzi, O. Kepp, C. Trojel-Hansen, and G. Kroemer
    EMBO Rep. 13, 322-330 (1 April 2012)

    Endoplasmic Reticulum Stress, the Unfolded Protein Response, Autophagy, and the Integrated Regulation of Breast Cancer Cell Fate
    R. Clarke, K. L. Cook, R. Hu, C. O. B. Facey, I. Tavassoly, J. L. Schwartz, W. T. Baumann, J. J. Tyson, J. Xuan, Y. Wang et al.
    Cancer Res. 72, 1321-1331 (15 March 2012)

    Kar2p availability defines distinct forms of endoplasmic reticulum stress in living cells
    P. Lajoie, R. D. Moir, I. M. Willis, and E. L. Snapp
    Mol. Biol. Cell 23, 955-964 (1 March 2012)

    Pim Kinase Inhibitors Sensitize Prostate Cancer Cells to Apoptosis Triggered by Bcl-2 Family Inhibitor ABT-737
    J. H. Song, and A. S. Kraft
    Cancer Res. 72, 294-303 (1 January 2012)

    Mechanisms of ER Stress-Induced Apoptosis in Atherosclerosis
    C. M. Scull, and I. Tabas
    Arterioscler. Thromb. Vasc. Bio. 31, 2792-2797 (1 December 2011)

    The Binding Protein BiP Attenuates Stress-Induced Cell Death in Soybean via Modulation of the N-Rich Protein-Mediated Signaling Pathway
    P. A. A. Reis, G. L. Rosado, L. A. C. Silva, L. C. Oliveira, L. B. Oliveira, M. D. L. Costa, F. C. Alvim, and E. P. B. Fontes
    Plant Physiol. 157, 1853-1865 (1 December 2011)

    BAX inhibitor-1 regulates autophagy by controlling the IRE1{alpha} branch of the unfolded protein response
    K. Castillo, D. Rojas-Rivera, F. Lisbona, B. Caballero, M. Nassif, F. A. Court, S. Schuck, C. Ibar, P. Walter, J. Sierralta et al.
    EMBO J. 30, 4465-4478 (2 November 2011)

    The Unfolded Protein Response: Integrating Stress Signals Through the Stress Sensor IRE1{alpha}
    C. Hetz, F. Martinon, D. Rodriguez, and L. H. Glimcher
    Physiol. Rev. 91, 1219-1243 (1 October 2011)

    Minocycline inhibits cell death and decreases mutant Huntingtin aggregation by targeting Apaf-1
    M. Sancho, A. E. Herrera, A. Gortat, R. J. Carbajo, A. Pineda-Lucena, M. Orzaez, and E. Perez-Paya
    Hum Mol Genet 20, 3545-3553 (15 September 2011)

    Membrane aberrancy and unfolded proteins activate the endoplasmic reticulum stress sensor Ire1 in different ways
    T. Promlek, Y. Ishiwata-Kimata, M. Shido, M. Sakuramoto, K. Kohno, and Y. Kimata
    Mol. Biol. Cell 22, 3520-3532 (15 September 2011)

    A Conserved Structural Determinant Located at the Interdomain Region of Mammalian Inositol-requiring Enzyme 1{alpha}
    Z. Xue, Y. He, K. Ye, Z. Gu, Y. Mao, and L. Qi
    J Biol Chem 286, 30859-30866 (2 September 2011)

    ER Stress and Its Functional Link to Mitochondria: Role in Cell Survival and Death
    J. D. Malhotra, and R. J. Kaufman
    Cold Spring Harb. Perspect. Biol. 3, a004424-a004424 (1 September 2011)

    Multiple BH3 Mimetics Antagonize Antiapoptotic MCL1 Protein by Inducing the Endoplasmic Reticulum Stress Response and Up-regulating BH3-only Protein NOXA
    T. C. Albershardt, B. L. Salerni, R. S. Soderquist, D. J. P. Bates, A. A. Pletnev, A. F. Kisselev, and A. Eastman
    J Biol Chem 286, 24882-24895 (15 July 2011)

    Potent and Selective Inhibitors of the Inositol-requiring Enzyme 1 Endoribonuclease
    K. Volkmann, J. L. Lucas, D. Vuga, X. Wang, D. Brumm, C. Stiles, D. Kriebel, A. Der-Sarkissian, K. Krishnan, C. Schweitzer et al.
    J Biol Chem 286, 12743-12755 (8 April 2011)

    The unfolded protein response transducer IRE1{alpha} prevents ER stress-induced hepatic steatosis
    K. Zhang, S. Wang, J. Malhotra, J. R. Hassler, S. H. Back, G. Wang, L. Chang, W. Xu, H. Miao, R. Leonardi et al.
    EMBO J. 30, 1357-1375 (6 April 2011)

    Bifunctional Apoptosis Regulator (BAR), an Endoplasmic Reticulum (ER)-associated E3 Ubiquitin Ligase, Modulates BI-1 Protein Stability and Function in ER Stress
    J. Rong, L. Chen, J. I. Toth, M. Tcherpakov, M. D. Petroski, and J. C. Reed
    J Biol Chem 286, 1453-1463 (14 January 2011)

    Escherichia coli Subtilase Cytotoxin Induces Apoptosis Regulated by Host Bcl-2 Family Proteins Bax/Bak
    K. L. May, J. C. Paton, and A. W. Paton
    Infect. Immun. 78, 4691-4696 (1 November 2010)

    Mammalian endoplasmic reticulum stress sensor IRE1 signals by dynamic clustering
    H. Li, A. V. Korennykh, S. L. Behrman, and P. Walter
    Proc. Natl. Acad. Sci. USA 107, 16113-16118 (14 September 2010)

    Molecular Symbiosis of CHOP and C/EBP{beta} Isoform LIP Contributes to Endoplasmic Reticulum Stress-Induced Apoptosis
    C.-B. Chiribau, F. Gaccioli, C. C. Huang, C. L. Yuan, and M. Hatzoglou
    Mol. Cell. Biol. 30, 3722-3731 (15 July 2010)

    Immunogenic Tumor Cell Death for Optimal Anticancer Therapy: The Calreticulin Exposure Pathway
    L. Zitvogel, O. Kepp, L. Senovilla, L. Menger, N. Chaput, and G. Kroemer
    Clin. Cancer Res. 16, 3100-3104 (15 June 2010)

    Regulation of basal cellular physiology by the homeostatic unfolded protein response
    D. T. Rutkowski, and R. S. Hegde
    JCB 189, 783-794 (31 May 2010)

    Rapamycin Inhibits Postprandial-Mediated X-Box-Binding Protein-1 Splicing in Rat Liver
    K. T. Pfaffenbach, A. M. Nivala, L. Reese, F. Ellis, D. Wang, Y. Wei, and M. J. Pagliassotti
    J. Nutr. 140, 879-884 (1 May 2010)

    Linking endoplasmic reticulum stress to cell death in hepatocytes: roles of C/EBP homologous protein and chemical chaperones in palmitate-mediated cell death
    K. T. Pfaffenbach, C. L. Gentile, A. M. Nivala, D. Wang, Y. Wei, and M. J. Pagliassotti
    Am. J. Physiol. Endocrinol. Metab. 298, E1027-E1035 (1 May 2010)

    The BCL-2 Protein BAK Is Required for Long-chain Ceramide Generation during Apoptosis
    L. J. Siskind, T. D. Mullen, K. Romero Rosales, C. J. Clarke, M. J. Hernandez-Corbacho, A. L. Edinger, and L. M. Obeid
    J Biol Chem 285, 11818-11826 (16 April 2010)

    MCP-1 causes cardiomyoblast death via autophagy resulting from ER stress caused by oxidative stress generated by inducing a novel zinc-finger protein, MCPIP
    C. W. Younce, and P. E. Kolattukudy
    Biochem. J. 426, 43-53 (15 February 2010)

    A Crucial Role for RACK1 in the Regulation of Glucose-Stimulated IRE1{alpha} Activation in Pancreatic {beta} Cells
    Y. Qiu, T. Mao, Y. Zhang, M. Shao, J. You, Q. Ding, Y. Chen, D. Wu, D. Xie, X. Lin et al.
    Sci Signal 3, ra7-ra7 (26 January 2010)

    Inhibition of the ER Ca2+ pump forces multidrug-resistant cells deficient in Bak and Bax into necrosis
    K. Janssen, S. Horn, M. T. Niemann, P. T. Daniel, K. Schulze-Osthoff, and U. Fischer
    J. Cell Sci. 122, 4481-4491 (15 December 2009)

    Nitrosative Stress-Induced S-Glutathionylation of Protein Disulfide Isomerase Leads to Activation of the Unfolded Protein Response
    D. M. Townsend, Y. Manevich, L. He, Y. Xiong, R. R. Bowers, S. Hutchens, and K. D. Tew
    Cancer Res. 69, 7626-7634 (1 October 2009)

    When separation means death: killing through the mitochondria, but starting from the endoplasmic reticulum
    V. Lamarca, and L. Scorrano
    EMBO J. 28, 1681-1683 (17 June 2009)

    Mitochondrial apoptosis induced by BH3-only molecules in the exclusive presence of endoplasmic reticular Bak
    M. Klee, K. Pallauf, S. Alcala, A. Fleischer, and F. X. Pimentel-Muinos
    EMBO J. 28, 1757-1768 (17 June 2009)

    ER stress protects from retinal degeneration
    C. S. Mendes, C. Levet, G. Chatelain, P. Dourlen, A. Fouillet, M.-L. Dichtel-Danjoy, A. Gambis, H. D. Ryoo, H. Steller, B. Mollereau et al.
    EMBO J. 28, 1296-1307 (6 May 2009)

    Dehydrocostuslactone, a Medicinal Plant-Derived Sesquiterpene Lactone, Induces Apoptosis Coupled to Endoplasmic Reticulum Stress in Liver Cancer Cells
    Y.-L. Hsu, L.-Y. Wu, and P.-L. Kuo
    J. Pharmacol. Exp. Ther. 329, 808-819 (1 May 2009)

    Bcl-2 family on guard at the ER
    E. Szegezdi, D. C. MacDonald, T. Ni Chonghaile, S. Gupta, and A. Samali
    Am. J. Physiol. Cell Physiol. 296, C941-C953 (1 May 2009)

    Mitochondrial degeneration and not apoptosis is the primary cause of embryonic lethality in ceramide transfer protein mutant mice
    X. Wang, R. P. Rao, T. Kosakowska-Cholody, M. A. Masood, E. Southon, H. Zhang, C. Berthet, K. Nagashim, T. K. Veenstra, L. Tessarollo et al.
    JCB 184, 143-158 (12 January 2009)

    Seipinopathy: a novel endoplasmic reticulum stress-associated disease
    D. Ito, and N. Suzuki
    Brain 132, 8-15 (1 January 2009)

    Tumor Necrosis Factor-{alpha} Can Provoke Cleavage and Activation of Sterol Regulatory Element-binding Protein in Ethanol-exposed Cells via a Caspase-dependent Pathway That Is Cholesterol Insensitive
    J. G. Pastorino, and N. Shulga
    J Biol Chem 283, 25638-25649 (12 September 2008)

    Protein Kinase C{theta} Is Required for Autophagy in Response to Stress in the Endoplasmic Reticulum
    K. Sakaki, J. Wu, and R. J. Kaufman
    J Biol Chem 283, 15370-15380 (30 May 2008)

    AIP1 Is Critical in Transducing IRE1-mediated Endoplasmic Reticulum Stress Response
    D. Luo, Y. He, H. Zhang, L. Yu, H. Chen, Z. Xu, S. Tang, F. Urano, and W. Min
    J Biol Chem 283, 11905-11912 (2 May 2008)

    Ricin Inhibits Activation of the Unfolded Protein Response by Preventing Splicing of the HAC1 mRNA
    B. A. Parikh, A. Tortora, X.-P. Li, and N. E. Tumer
    J Biol Chem 283, 6145-6153 (7 March 2008)

    Unfolded protein response transcription factor XBP-1 does not influence prion replication or pathogenesis
    C. Hetz, A.-H. Lee, D. Gonzalez-Romero, P. Thielen, J. Castilla, C. Soto, and L. H. Glimcher
    Proc. Natl. Acad. Sci. USA 105, 757-762 (15 January 2008)

    Critical Role of the Stress Chaperone GRP78/BiP in Tumor Proliferation, Survival, and Tumor Angiogenesis in Transgene-Induced Mammary Tumor Development
    D. Dong, M. Ni, J. Li, S. Xiong, W. Ye, J. J. Virrey, C. Mao, R. Ye, M. Wang, L. Pen et al.
    Cancer Res. 68, 498-505 (15 January 2008)

    Integrated Endoplasmic Reticulum Stress Responses in Cancer
    M. Moenner, O. Pluquet, M. Bouchecareilh, and E. Chevet
    Cancer Res. 67, 10631-10634 (15 November 2007)

    A New Road to Induce Heme Oxygenase-1 Expression by Carbon Monoxide
    H. P. Kim, and A. M.K. Choi
    Circ. Res. 101, 862-864 (26 October 2007)

    Inhibition of MEK Sensitizes Human Melanoma Cells to Endoplasmic Reticulum Stress-Induced Apoptosis
    C. C. Jiang, L. H. Chen, S. Gillespie, Y. F. Wang, K. A. Kiejda, X. D. Zhang, and P. Hersey
    Cancer Res. 67, 9750-9761 (15 October 2007)

    The transcription factor XBP-1 is essential for the development and survival of dendritic cells
    N. N. Iwakoshi, M. Pypaert, and L. H. Glimcher
    JEM 204, 2267-2275 (1 October 2007)

    Breast Cancer Cell Proliferation Is Inhibited by BAD: REGULATION OF CYCLIN D1
    R. Fernando, J. S. Foster, A. Bible, A. Strom, R. G. Pestell, M. Rao, A. Saxton, S. J. Baek, K. Yamaguchi, R. Donnell et al.
    J Biol Chem 282, 28864-28873 (28 September 2007)

    The Kinase Inhibitor Sorafenib Induces Cell Death through a Process Involving Induction of Endoplasmic Reticulum Stress
    M. Rahmani, E. M. Davis, T. R. Crabtree, J. R. Habibi, T. K. Nguyen, P. Dent, and S. Grant
    Mol. Cell. Biol. 27, 5499-5513 (1 August 2007)

    STAT1 Activation Causes Translocation of Bax to the Endoplasmic Reticulum during the Resolution of Airway Mucous Cell Hyperplasia by IFN-{gamma}
    B. A. Stout, K. Melendez, J. Seagrave, M. J. Holtzman, B. Wilson, J. Xiang, and Y. Tesfaigzi
    J. Immunol. 178, 8107-8116 (15 June 2007)

    Endoplasmic Reticulum Stress: Signaling the Unfolded Protein Response
    E. Lai, T. Teodoro, and A. Volchuk
    Physiology 22, 193-201 (1 June 2007)

    Interaction of a Cyclin E Fragment with Ku70 Regulates Bax-Mediated Apoptosis
    S. Mazumder, D. Plesca, M. Kinter, and A. Almasan
    Mol. Cell. Biol. 27, 3511-3520 (1 May 2007)

    Perturbation of Endoplasmic Reticulum Homeostasis Facilitates Prion Replication
    C. Hetz, J. Castilla, and C. Soto
    J Biol Chem 282, 12725-12733 (27 April 2007)

    Endoplasmic Reticulum Stress Inhibition Protects against Excitotoxic Neuronal Injury in the Rat Brain
    A.-L. Sokka, N. Putkonen, G. Mudo, E. Pryazhnikov, S. Reijonen, L. Khiroug, N. Belluardo, D. Lindholm, and L. Korhonen
    J. Neurosci. 27, 901-908 (24 January 2007)

    Characterization of Host Cell Death Induced by Chlamydia trachomatis
    S. Ying, S. F. Fischer, M. Pettengill, D. Conte, S. A. Paschen, D. M. Ojcius, and G. Hacker
    Infect. Immun. 74, 6057-6066 (1 November 2006)

    Mediators of endoplasmic reticulum stress-induced apoptosis
    E. Szegezdi, S. E. Logue, A. M. Gorman, and A. Samali
    EMBO Rep. 7, 880-885 (1 September 2006)

    Cell biology. Stressed cells cope with protein overload.
    D. Ron, S. E. Logue, A. M. Gorman, and A. Samali
    Science 313, 52-53 (7 July 2006)

    "Translating" Tumor Hypoxia: Unfolded Protein Response (UPR)-Dependent and UPR-Independent Pathways
    C. Koumenis, and B. G. Wouters
    Mol Cancer Res 4, 423-436 (1 July 2006)

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