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Science 28 January 2000:
Vol. 287. no. 5453, pp. 664 - 666
DOI: 10.1126/science.287.5453.664
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Reports

Coupling of Stress in the ER to Activation of JNK Protein Kinases by Transmembrane Protein Kinase IRE1

Fumihiko Urano, XiaoZhong Wang, Anne Bertolotti, Yuhong Zhang, Peter Chung, Heather P. Harding, David Ron *

Malfolded proteins in the endoplasmic reticulum (ER) induce cellular stress and activate c-Jun amino-terminal kinases (JNKs or SAPKs). Mammalian homologs of yeast IRE1, which activate chaperone genes in response to ER stress, also activated JNK, and IRE1alpha -/- fibroblasts were impaired in JNK activation by ER stress. The cytoplasmic part of IRE1 bound TRAF2, an adaptor protein that couples plasma membrane receptors to JNK activation. Dominant-negative TRAF2 inhibited activation of JNK by IRE1. Activation of JNK by endogenous signals initiated in the ER proceeds by a pathway similar to that initiated by cell surface receptors in response to extracellular signals.

Skirball Institute of Biomolecular Medicine, Departments of Medicine, Cell Biology and the Kaplan Cancer Center, New York University Medical School, New York, NY 10016, USA.
*   To whom correspondence should be addressed: E-mail: ron{at}saturn.med.nyu.edu

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Mol. Pharmacol. 67, 1684-1689
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Tumor Necrosis Factor {alpha}-induced Desumoylation and Cytoplasmic Translocation of Homeodomain-interacting Protein Kinase 1 Are Critical for Apoptosis Signal-regulating Kinase 1-JNK/p38 Activation.
X. Li, R. Zhang, D. Luo, S.-J. Park, Q. Wang, Y. Kim, and W. Min (2005)
J. Biol. Chem. 280, 15061-15070
   Abstract »    Full Text »    PDF »
Genomic Discovery Reveals a Molecular System for Resistance to Oxidative and Endoplasmic Reticulum Stress in Cultured Glioma.
H. M. Fathallah-Shaykh (2005)
Arch Neurol 62, 233-236
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Cytokines Downregulate the Sarcoendoplasmic Reticulum Pump Ca2+ ATPase 2b and Deplete Endoplasmic Reticulum Ca2+, Leading to Induction of Endoplasmic Reticulum Stress in Pancreatic {beta}-Cells.
A. K. Cardozo, F. Ortis, J. Storling, Y.-M. Feng, J. Rasschaert, M. Tonnesen, F. Van Eylen, T. Mandrup-Poulsen, A. Herchuelz, and D. L. Eizirik (2005)
Diabetes 54, 452-461
   Abstract »    Full Text »    PDF »
NAD(P)H Oxidase Nox-4 Mediates 7-Ketocholesterol-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Aortic Smooth Muscle Cells.
E. Pedruzzi, C. Guichard, V. Ollivier, F. Driss, M. Fay, C. Prunet, J.-C. Marie, C. Pouzet, M. Samadi, C. Elbim, et al. (2004)
Mol. Cell. Biol. 24, 10703-10717
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Protein-tyrosine Phosphatase 1B Potentiates IRE1 Signaling during Endoplasmic Reticulum Stress.
F. Gu, D. T. Nguyen, M. Stuible, N. Dube, M. L. Tremblay, and E. Chevet (2004)
J. Biol. Chem. 279, 49689-49693
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Critical Role of Endogenous Akt/IAPs and MEK1/ERK Pathways in Counteracting Endoplasmic Reticulum Stress-induced Cell Death.
P. Hu, Z. Han, A. D. Couvillon, and J. H. Exton (2004)
J. Biol. Chem. 279, 49420-49429
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CHOP Is Involved in Endoplasmic Reticulum Stress-induced Apoptosis by Enhancing DR5 Expression in Human Carcinoma Cells.
H. Yamaguchi and H.-G. Wang (2004)
J. Biol. Chem. 279, 45495-45502
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Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes.
U. Ozcan, Q. Cao, E. Yilmaz, A.-H. Lee, N. N. Iwakoshi, E. Ozdelen, G. Tuncman, C. Gorgun, L. H. Glimcher, and G. S. Hotamisligil (2004)
Science 306, 457-461
   Abstract »    Full Text »    PDF »
Dilated Cardiomyopathy Caused by Aberrant Endoplasmic Reticulum Quality Control in Mutant KDEL Receptor Transgenic Mice.
H. Hamada, M. Suzuki, S. Yuasa, N. Mimura, N. Shinozuka, Y. Takada, M. Suzuki, T. Nishino, H. Nakaya, H. Koseki, et al. (2004)
Mol. Cell. Biol. 24, 8007-8017
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Effect on Tumor Cells of Blocking Survival Response to Glucose Deprivation.
H.-R. Park, A. Tomida, S. Sato, Y. Tsukumo, J. Yun, T. Yamori, Y. Hayakawa, T. Tsuruo, and K. Shin-ya (2004)
J Natl Cancer Inst 96, 1300-1310
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The ASK1-MAP Kinase Cascades in Mammalian Stress Response.
J. Matsukawa, A. Matsuzawa, K. Takeda, and H. Ichijo (2004)
J. Biochem. 136, 261-265
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Nck-dependent Activation of Extracellular Signal-regulated Kinase-1 and Regulation of Cell Survival during Endoplasmic Reticulum Stress.
D. T. Nguyen, S. Kebache, A. Fazel, H. N. Wong, S. Jenna, A. Emadali, E.-h. Lee, J. J.M. Bergeron, R. J. Kaufman, L. Larose, et al. (2004)
Mol. Biol. Cell 15, 4248-4260
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Herp Stabilizes Neuronal Ca2+ Homeostasis and Mitochondrial Function during Endoplasmic Reticulum Stress.
S. L. Chan, W. Fu, P. Zhang, A. Cheng, J. Lee, K. Kokame, and M. P. Mattson (2004)
J. Biol. Chem. 279, 28733-28743
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Signaling the Unfolded Protein Response from the Endoplasmic Reticulum.
K. Zhang and R. J. Kaufman (2004)
J. Biol. Chem. 279, 25935-25938
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Thioredoxin-2 Inhibits Mitochondria-Located ASK1-Mediated Apoptosis in a JNK-Independent Manner.
R. Zhang, R. Al-Lamki, L. Bai, J. W. Streb, J. M. Miano, J. Bradley, and W. Min (2004)
Circ. Res. 94, 1483-1491
   Abstract »    Full Text »    PDF »
A Cellular UDP-glucose Deficiency Causes Overexpression of Glucose/Oxygen-regulated Proteins Independent of the Endoplasmic Reticulum Stress Elements.
M. Flores-Diaz, J.-C. Higuita, I. Florin, T. Okada, P. Pollesello, T. Bergman, M. Thelestam, K. Mori, and A. Alape-Giron (2004)
J. Biol. Chem. 279, 21724-21731
   Abstract »    Full Text »    PDF »


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